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Genetic studies of systemic lupus erythematosus in Asia: where are we now?

Genes & Immunity volume 10, pages 421–432 (2009)Cite this article

Abstract

There have been many genetic studies of systemic lupus erythematosus (SLE) in Asia, but the status of SLE in Asia remains unclear. Genes that have been associated with SLE in Caucasians have shown both consistent and inconsistent results in Asians. This prompted us to review studies of SLE-associated genes and compare the degree of consistency according to ethnicity in Asia. We searched PubMed and the national databases in Korea and Japan for SLE genetic studies. A total of 755 articles were found and after applying various exclusion criteria, 442 studies including 17 linkage studies, 2 genome-wide association studies and 423 candidate-gene analyses were reviewed. Nine linkage loci were confirmed to be associated with SLE susceptibility in non-Asians, but the risk locus (16q12) has been identified in only one Asian study. A total of 156 candidate genes were analyzed, of which 92 were studied in Asians. Although there were allelic (HLA-DRB1 and IRF5) or genetic heterogeneity (FCGR gene family), HLA-DRB1, the FCGR gene family, IRF5, STAT4 and MECP2 showed consistent associations with SLE susceptibility across ethnicities. In conclusion, genetic associations often vary with ethnicity, requiring validation in different ethnic groups, and hence future SLE genetic studies will require strong worldwide collaborations.

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References

  1. Sillanpaa MJ, Auranen K . Replication in genetic studies of complex traits. Ann Hum Genet 2004; 68 (Part 6): 646–657.

    CAS  Google Scholar 

  2. Sestak AL, Nath SK, Sawalha AH, Harley JB . Current status of lupus genetics. Arthritis Res Ther 2007; 9: 210.

    Google Scholar 

  3. Feng XB, Shen N, Chen SL, Qian J, Wu H, Bao CD et al. [Susceptibility gene of systemic lupus erythematosus in 16q12 in Chinese cohort]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2003; 20: 27–30.

    CAS  Google Scholar 

  4. Fronek Z, Timmerman LA, Alper CA, Hahn BH, Kalunian K, Peterlin BM et al. Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus. Arthritis Rheum 1990; 33: 1542–1553.

    CAS  Google Scholar 

  5. Yao Z, Kimura A, Hartung K, Haas PJ, Volgger A, Brunnler G et al. Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP, DQA1, DQB1 haplotypes in systemic lupus erythematosus. SLE Study Group members. Immunogenetics 1993; 38: 421–429.

    CAS  Google Scholar 

  6. So AK, Fielder AH, Warner CA, Isenberg DA, Batchelor JR, Walport MJ . DNA polymorphism of major histocompatibility complex class II and class III genes in systemic lupus erythematosus. Tissue Antigens 1990; 35: 144–147.

    CAS  Google Scholar 

  7. van der Linden MW, van der Slik AR, Zanelli E, Giphart MJ, Pieterman E, Schreuder GM et al. Six microsatellite markers on the short arm of chromosome 6 in relation to HLA-DR3 and TNF-308A in systemic lupus erythematosus. Genes Immun 2001; 2: 373–380.

    CAS  Google Scholar 

  8. Rood MJ, van Krugten MV, Zanelli E, van der Linden MW, Keijsers V, Schreuder GM et al. TNF-308A and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus. Arthritis Rheum 2000; 43: 129–134.

    CAS  Google Scholar 

  9. Tjernstrom F, Hellmer G, Nived O, Truedsson L, Sturfelt G . Synergetic effect between interleukin-1 receptor antagonist allele (IL1RN*2) and MHC class II (DR17,DQ2) in determining susceptibility to systemic lupus erythematosus. Lupus 1999; 8: 103–108.

    CAS  Google Scholar 

  10. Cowland JB, Andersen V, Halberg P, Morling N . DNA polymorphism of HLA class II genes in systemic lupus erythematosus. Tissue Antigens 1994; 43: 34–37.

    CAS  Google Scholar 

  11. Reinharz D, Tiercy JM, Mach B, Jeannet M . Absence of DRw15/3 and of DRw15/7 heterozygotes in Caucasian patients with systemic lupus erythematosus. Tissue Antigens 1991; 37: 10–15.

    CAS  Google Scholar 

  12. Vargas-Alarcon G, Granados J, Martinez-Laso J, Gomez-Casado E, Zuniga J, Salgado N et al. Lack of association between the polymorphism at the heat-shock protein (HSP70-2) gene and systemic lupus erythematosus (SLE) in the Mexican mestizo population. Genes Immun 2000; 1: 367–370.

    CAS  Google Scholar 

  13. Tian W, Li LX, Guo SS . Correlative study on HLA-DR2 allelic polymorphism and systemic lupus erythematosus in the Han nationality in Hunan province]. Hunan Yi Ke Da Xue Xue Bao 2000; 25: 15–17.

    CAS  Google Scholar 

  14. Zhang J, Ai R, Chow F . The polymorphisms of HLA-DR and TNF B loci in northern Chinese Han nationality and susceptibility to systemic lupus erythematosus. Chin Med Sci J 1997; 12: 107–110.

    CAS  Google Scholar 

  15. Zhang J, Zhou F, Ai R . [Study on some susceptible genes of systemic lupus erythematosus in Han nationality of China]. Zhonghua Nei Ke Za Zhi 1996; 35: 19–22.

    CAS  Google Scholar 

  16. Doherty DG, Ireland R, Demaine AG, Wang F, Veerapan K, Welsh KI et al. Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus in southern Chinese. Arthritis Rheum 1992; 35: 641–646.

    CAS  Google Scholar 

  17. Wang M, Dong Y, Huang S . [Study on the association between tumor necrosis factor alpha gene polymorphism and systemic lupus erythematosus]. Zhonghua Nei Ke Za Zhi 1999; 38: 393–396.

    CAS  Google Scholar 

  18. Azizah MR, Ainol SS, Kong NC, Normaznah Y, Rahim MN . HLA antigens in Malay patients with systemic lupus erythematosus: association with clinical and autoantibody expression. Korean J Intern Med 2001; 16: 123–131.

    CAS  Google Scholar 

  19. Hong GH, Kim HY, Takeuchi F, Nakano K, Yamada H, Matsuta K et al. Association of complement C4 and HLA-DR alleles with systemic lupus erythematosus in Koreans. J Rheumatol 1994; 21: 442–447.

    CAS  Google Scholar 

  20. Lee HS, Chung YH, Kim TG, Kim TH, Jun JB, Jung S et al. Independent association of HLA-DR and FC gamma receptor polymorphisms in Korean patients with systemic lupus erythematosus. Rheumatology (Oxford) 2003; 42: 1501–1507.

    CAS  Google Scholar 

  21. Kim HY, Lee SH, Yang HI, Park SH, Cho CS, Kim TG et al. TNFB gene polymorphism in patients with systemic lupus erythematosus in Korean. Korean J Intern Med 1995; 10: 130–136.

    CAS  Google Scholar 

  22. Kim TG, Kim HY, Lee SH, Cho CS, Park SH, Choi HB et al. Systemic lupus erythematosus with nephritis is strongly associated with the TNFB*2 homozygote in the Korean population. Hum Immunol 1996; 46: 10–17.

    CAS  Google Scholar 

  23. Li CF, He XH, Teng Q, Jiang ZF . Association of HLA-A, B, and DR haplotypes with genotype in Chinese children with systemic lupus erythematosus]. Zhonghua Er Ke Za Zhi 2003; 41: 422–425.

    Google Scholar 

  24. Vargas-Alarcon G, Salgado N, Granados J, Gomez-Casado E, Martinez-Laso J, Alcocer-Varela J et al. Class II allele and haplotype frequencies in Mexican systemic lupus erythematosus patients: the relevance of considering homologous chromosomes in determining susceptibility. Hum Immunol 2001; 62: 814–820.

    CAS  Google Scholar 

  25. Hrycek A, Siekiera U, Cieslik P, Szkrobka W . HLA-DRB1 and -DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus. Rheumatol Int 2005; 26: 1–6.

    CAS  Google Scholar 

  26. Arnett FC, Olsen ML, Anderson KL, Reveille JD . Molecular analysis of major histocompatibility complex alleles associated with the lupus anticoagulant. J Clin Invest 1991; 87: 1490–1495.

    CAS  Google Scholar 

  27. Hauptmann G, Tappeiner G, Schifferli JA . Inherited deficiency of the fourth component of human complement. Immunodefic Rev 1988; 1: 3–22.

    CAS  Google Scholar 

  28. Jonsen A, Bengtsson AA, Sturfelt G, Truedsson L . Analysis of HLA DR, HLA DQ, C4A, FcgammaRIIa, FcgammaRIIIa, MBL, and IL-1Ra allelic variants in Caucasian systemic lupus erythematosus patients suggests an effect of the combined FcgammaRIIa R/R and IL-1Ra 2/2 genotypes on disease susceptibility. Arthritis Res Ther 2004; 6: R557–R562.

    CAS  Google Scholar 

  29. Fielder AH, Walport MJ, Batchelor JR, Rynes RI, Black CM, Dodi IA et al. Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility. Br Med J (Clin Res Ed) 1983; 286: 425–428.

    CAS  Google Scholar 

  30. Olsen ML, Goldstein R, Arnett FC, Duvic M, Pollack M, Reveille JD . C4A gene deletion and HLA associations in black Americans with systemic lupus erythematosus. Immunogenetics 1989; 30: 27–33.

    CAS  Google Scholar 

  31. Rantapaa Dahlqvist S, Beckman G, Beckman L . Serum protein markers in systemic lupus erythematosus. Hum Hered 1988; 38: 44–47.

    CAS  Google Scholar 

  32. Skarsvag S . The importance of C4A null genes in Norwegian patients with systemic lupus erythematosus. Scand J Immunol 1995; 42: 572–576.

    CAS  Google Scholar 

  33. Huang DF, Siminovitch KA, Liu XY, Olee T, Olsen NJ, Berry C et al. Population and family studies of three disease-related polymorphic genes in systemic lupus erythematosus. J Clin Invest 1995; 95: 1766–1772.

    CAS  Google Scholar 

  34. Fan Q, Uring-Lambert B, Weill B, Gautreau C, Menkes CJ, Delpech M . Complement component C4 deficiencies and gene alterations in patients with systemic lupus erythematosus. Eur J Immunogenet 1993; 20: 11–21.

    CAS  Google Scholar 

  35. Dunckley H, Gatenby PA, Hawkins B, Naito S, Serjeantson SW . Deficiency of C4A is a genetic determinant of systemic lupus erythematosus in three ethnic groups. J Immunogenet 1987; 14: 209–218.

    CAS  Google Scholar 

  36. Yamada H, Watanabe A, Mimori A, Nakano K, Takeuchi F, Matsuta K et al. Lack of gene deletion for complement C4A deficiency in Japanese patients with systemic lupus erythematosus. J Rheumatol 1990; 17: 1054–1057.

    CAS  Google Scholar 

  37. Man XY, Luo HR, Li XP, Yao YG, Mao CZ, Zhang YP . Polymerase chain reaction based C4AQ0 and C4BQ0 genotyping: association with systemic lupus erythematosus in southwest Han Chinese. Ann Rheum Dis 2003; 62: 71–73.

    CAS  Google Scholar 

  38. Puah SM, Lian LH, Chew CH, Chua KH, Tan SY . A study of association of the complement C4 mutations with systemic lupus erythematosus in the Malaysian population. Lupus 2007; 16: 750–754.

    CAS  Google Scholar 

  39. Hartung K, Baur MP, Coldewey R, Fricke M, Kalden JR, Lakomek HJ et al. Major histocompatibility complex haplotypes and complement C4 alleles in systemic lupus erythematosus. Results of a multicenter study. J Clin Invest 1992; 90: 1346–1351.

    CAS  Google Scholar 

  40. Correa PA, Molina JF, Pinto LF, Arcos-Burgos M, Herrera M, Anaya JM . TAP1 and TAP2 polymorphisms analysis in northwestern Colombian patients with systemic lupus erythematosus. Ann Rheum Dis 2003; 62: 363–365.

    CAS  Google Scholar 

  41. Davies EJ, Donn RP, Hillarby MC, Grennan DM, Ollier WE . Polymorphisms of the TAP2 transporter gene in systemic lupus erythematosus. Ann Rheum Dis 1994; 53: 61–63.

    CAS  Google Scholar 

  42. Huang CM, Hang LW, Chen CL, Wu JY, Tsai FJ . Polymorphisms of TAP1 transporter genes in Chinese patients with systemic lupus erythematosus in Taiwan. Rheumatol Int 2004; 24: 130–132.

    Google Scholar 

  43. Takeuchi F, Nakano K, Nabeta H, Hong GH, Kuwata S, Ito K . Polymorphisms of the TAP1 and TAP2 transporter genes in Japanese SLE. Ann Rheum Dis 1996; 55: 924–926.

    CAS  Google Scholar 

  44. Suarez A, Lopez P, Mozo L, Gutierrez C . Differential effect of IL10 and TNF{alpha} genotypes on determining susceptibility to discoid and systemic lupus erythematosus. Ann Rheum Dis 2005; 64: 1605–1610.

    CAS  Google Scholar 

  45. Sullivan KE, Wooten C, Schmeckpeper BJ, Goldman D, Petri MA . A promoter polymorphism of tumor necrosis factor alpha associated with systemic lupus erythematosus in African-Americans. Arthritis Rheum 1997; 40: 2207–2211.

    CAS  Google Scholar 

  46. Zuniga J, Vargas-Alarcon G, Hernandez-Pacheco G, Portal-Celhay C, Yamamoto-Furusho JK, Granados J . Tumor necrosis factor-alpha promoter polymorphisms in Mexican patients with systemic lupus erythematosus (SLE). Genes Immun 2001; 2: 363–366.

    CAS  Google Scholar 

  47. Hirankarn N, Avihingsanon Y, Wongpiyabovorn J . Genetic susceptibility to SLE is associated with TNF-alpha gene polymorphism −863, but not −308 and −238, in Thai population. Int J Immunogenet 2007; 34: 425–430.

    CAS  Google Scholar 

  48. Lee YH, Harley JB, Nath SK . Meta-analysis of TNF-alpha promoter −308 A/G polymorphism and SLE susceptibility. Eur J Hum Genet 2006; 14: 364–371.

    CAS  Google Scholar 

  49. Bettinotti MP, Hartung K, Deicher H, Messer G, Keller E, Weiss EH et al. Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus: TNFB-MHC haplotypes. Immunogenetics 1993; 37: 449–454.

    CAS  Google Scholar 

  50. Takeuchi F, Nakano K, Nabeta H, Hong GH, Kawasugi K, Mori M et al. Genetic contribution of the tumour necrosis factor (TNF) B + 252*2/2 genotype, but not the TNFa,b microsatellite alleles, to systemic lupus erythematosus in Japanese patients. Int J Immunogenet 2005; 32: 173–178.

    CAS  Google Scholar 

  51. Wang Y, Zhang Y, Zhu S . [The association of sasceptibility of SLE and the gene polymorphism of TNF]. Zhonghua Yi Xue Za Zhi 1998; 78: 111–114.

    CAS  Google Scholar 

  52. Lu LY, Cheng HH, Sung PK, Tai MH, Yeh JJ, Chen A . Tumor necrosis factor-beta +252A polymorphism is associated with systemic lupus erythematosus in Taiwan. J Formos Med Assoc 2005; 104: 563–570.

    CAS  Google Scholar 

  53. Groh V, Bahram S, Bauer S, Herman A, Beauchamp M, Spies T . Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci USA 1996; 93: 12445–12450.

    CAS  Google Scholar 

  54. Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T . Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci USA 1999; 96: 6879–6884.

    CAS  Google Scholar 

  55. Gambelunghe G, Gerli R, Bocci EB, Del Sindaco P, Ghaderi M, Sanjeevi CB et al. Contribution of MHC class I chain-related A (MICA) gene polymorphism to genetic susceptibility for systemic lupus erythematosus. Rheumatology (Oxford) 2005; 44: 287–292.

    CAS  Google Scholar 

  56. Sanchez E, Torres B, Vilches JR, Lopez-Nevot MA, Ortego-Centeno N, Jimenez-Alonso J et al. No primary association of MICA polymorphism with systemic lupus erythematosus. Rheumatology (Oxford) 2006; 45: 1096–1100.

    CAS  Google Scholar 

  57. Ban G, Chu J, Mao C, Yang Z, Xu S, Chu Z et al. [A study of the relationship between MICA gene and systemic lupus erythematosus]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2002; 19: 298–301.

    CAS  Google Scholar 

  58. Muhlethaler-Mottet A, Otten LA, Steimle V, Mach B . Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator CIITA. EMBO J 1997; 16: 2851–2860.

    CAS  Google Scholar 

  59. Akkad DA, Jagiello P, Szyld P, Goedde R, Wieczorek S, Gross WL et al. Promoter polymorphism rs3087456 in the MHC class II transactivator gene is not associated with susceptibility for selected autoimmune diseases in German patient groups. Int J Immunogenet 2006; 33: 59–61.

    CAS  Google Scholar 

  60. Okamoto H, Kaneko H, Terai C, Kamatani N . Protective effect of A at position—168 in the type III promoter of the MHCIITA gene in systemic lupus erythematosus. Ann Rheum Dis 2007; 66: 1263–1264.

    Google Scholar 

  61. Linga-Reddy MV, Gunnarsson I, Svenungsson E, Sturfelt G, Jonsen A, Truedsson L et al. A polymorphic variant in the MHC2TA gene is not associated with systemic lupus erythematosus. Tissue Antigens 2007; 70: 412–414.

    CAS  Google Scholar 

  62. Sanchez E, Sabio JM, Jimenez-Alonso J, Callejas JL, Camps M, de Ramon E et al. Study of two polymorphisms of the MHC2TA gene with systemic lupus erythematosus. Rheumatology (Oxford) 2008; 47: 102–103.

    CAS  Google Scholar 

  63. Sullivan KE . Genetics of systemic lupus erythematosus. Clinical implications. Rheum Dis Clin North Am 2000; 26: 229–256, v–vi.

    CAS  Google Scholar 

  64. Tsao BP, Grossman JM . Genetics and systemic lupus erythematosus. Curr Rheumatol Rep 2001; 3: 183–190.

    CAS  Google Scholar 

  65. Yun HR, Koh HK, Kim SS, Chung WT, Kim DW, Hong KP et al. FcgammaRIIa/IIIa polymorphism and its association with clinical manifestations in Korean lupus patients. Lupus 2001; 10: 466–472.

    CAS  Google Scholar 

  66. Song YW, Han CW, Kang SW, Baek HJ, Lee EB, Shin CH et al. Abnormal distribution of Fc gamma receptor type IIa polymorphisms in Korean patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41: 421–426.

    CAS  Google Scholar 

  67. Sato H, Iwano M, Akai Y, Nishino T, Fujimoto T, Shiiki H et al. FcgammaRIIa polymorphism in Japanese patients with systemic lupus erythematosus. Lupus 2001; 10: 97–101.

    CAS  Google Scholar 

  68. Hirankarn N, Wongpiyabovorn J, Hanvivatvong O, Netsawang J, Akkasilpa S, Wongchinsri J et al. The synergistic effect of FC gamma receptor IIa and interleukin-10 genes on the risk to develop systemic lupus erythematosus in Thai population. Tissue Antigens 2006; 68: 399–406.

    CAS  Google Scholar 

  69. Khoa PD, Sugiyama T, Yokochi T . Fc gamma receptor II polymorphism in Vietnamese patients with systemic lupus erythematosus. Lupus 2003; 12: 704–706.

    CAS  Google Scholar 

  70. Salmon JE, Ng S, Yoo DH, Kim TH, Kim SY, Song GG . Altered distribution of Fc gamma receptor IIIA alleles in a cohort of Korean patients with lupus nephritis. Arthritis Rheum 1999; 42: 818–819.

    CAS  Google Scholar 

  71. Chen JY, Wang CM, Tsao KC, Chow YH, Wu JM, Li CL et al. Fc gamma receptor IIa, IIIa, and IIIb polymorphisms of systemic lupus erythematosus in Taiwan. Ann Rheum Dis 2004; 63: 877–880.

    CAS  Google Scholar 

  72. Hatta Y, Tsuchiya N, Ohashi J, Matsushita M, Fujiwara K, Hagiwara K et al. Association of Fc gamma receptor IIIB, but not of Fc gamma receptor IIA and IIIA polymorphisms with systemic lupus erythematosus in Japanese. Genes Immun 1999; 1: 53–60.

    CAS  Google Scholar 

  73. Kyogoku C, Dijstelbloem HM, Tsuchiya N, Hatta Y, Kato H, Yamaguchi A et al. Fc gamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Arthritis Rheum 2002; 46: 1242–1254.

    CAS  Google Scholar 

  74. Siriboonrit U, Tsuchiya N, Sirikong M, Kyogoku C, Bejrachandra S, Suthipinittharm P et al. Association of Fc gamma receptor IIb and IIIb polymorphisms with susceptibility to systemic lupus erythematosus in Thais. Tissue Antigens 2003; 61: 374–383.

    CAS  Google Scholar 

  75. Chu ZT, Tsuchiya N, Kyogoku C, Ohashi J, Qian YP, Xu SB et al. Association of Fc gamma receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations. Tissue Antigens 2004; 63: 21–27.

    CAS  Google Scholar 

  76. Lee EB, Lee YJ, Baek HJ, Kang SW, Chung ES, Shin CH et al. Fc gamma receptor IIIA polymorphism in Korean patients with systemic lupus erythematosus. Rheumatol Int 2002; 21: 222–226.

    CAS  Google Scholar 

  77. Karassa FB, Trikalinos TA, Ioannidis JP . The role of FcgammaRIIA and IIIA polymorphisms in autoimmune diseases. Biomed Pharmacother 2004; 58: 286–291.

    CAS  Google Scholar 

  78. Karassa FB, Trikalinos TA, Ioannidis JP . Role of the Fc gamma receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis. Arthritis Rheum 2002; 46: 1563–1571.

    CAS  Google Scholar 

  79. Karassa FB, Trikalinos TA, Ioannidis JP . The Fc gamma RIIIA-F158 allele is a risk factor for the development of lupus nephritis: a meta-analysis. Kidney Int 2003; 63: 1475–1482.

    CAS  Google Scholar 

  80. Chen JY, Wang CM, Ma CC, Luo SF, Edberg JC, Kimberly RP et al. Association of a transmembrane polymorphism of Fc gamma receptor IIb (FCGR2B) with systemic lupus erythematosus in Taiwanese patients. Arthritis Rheum 2006; 54: 3908–3917.

    CAS  Google Scholar 

  81. Pan F, Zhang K, Li X, Xu J, Hao J, Ye D . Association of Fc gamma receptor IIB gene polymorphism with genetic susceptibility to systemic lupus erythematosus in Chinese populations—a family-based association study. J Dermatol Sci 2006; 43: 35–41.

    CAS  Google Scholar 

  82. Pan F, Ye D, Zhang K, Li X, Xu J, Chen H . Gln50Ter Polymorphism of Fc gamma receptor IIB gene associated with genetic susceptibility to human systemic lupus erythematosus in Chinese populations. Arch Dermatol Res 2007; 299: 47–51.

    CAS  Google Scholar 

  83. Blank MC, Stefanescu RN, Masuda E, Marti F, King PD, Redecha PB et al. Decreased transcription of the human FCGR2B gene mediated by the −343 G/C promoter polymorphism and association with systemic lupus erythematosus. Hum Genet 2005; 117: 220–227.

    CAS  Google Scholar 

  84. Su K, Wu J, Edberg JC, Li X, Ferguson P, Cooper GS et al. A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. J Immunol 2004; 172: 7186–7191.

    CAS  Google Scholar 

  85. Kyogoku C, Tsuchiya N, Wu H, Tsao BP, Tokunaga K . Association of Fc gamma receptor IIA, but not IIB and IIIA, polymorphisms with systemic lupus erythematosus: a family-based association study in Caucasians. Arthritis Rheum 2004; 50: 671–673.

    CAS  Google Scholar 

  86. Magnusson V, Johanneson B, Lima G, Odeberg J, Alarcon-Segovia D, Alarcon-Riquelme ME . Both risk alleles for FcgammaRIIA and FcgammaRIIIA are susceptibility factors for SLE: a unifying hypothesis. Genes Immun 2004; 5: 130–137.

    CAS  Google Scholar 

  87. Li X, Wu J, Carter RH, Edberg JC, Su K, Cooper GS et al. A novel polymorphism in the Fc gamma receptor IIB (CD32B) transmembrane region alters receptor signaling. Arthritis Rheum 2003; 48: 3242–3252.

    CAS  Google Scholar 

  88. Magnusson V, Zunec R, Odeberg J, Sturfelt G, Truedsson L, Gunnarsson I et al. Polymorphisms of the Fc gamma receptor type IIB gene are not associated with systemic lupus erythematosus in the Swedish population. Arthritis Rheum 2004; 50: 1348–1350.

    CAS  Google Scholar 

  89. Kochi Y, Yamada R, Suzuki A, Harley JB, Shirasawa S, Sawada T et al. A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nat Genet 2005; 37: 478–485.

    CAS  Google Scholar 

  90. Choi CB, Kang CP, Seong SS, Bae SC, Kang C . The −169C/T polymorphism in FCRL3 is not associated with susceptibility to rheumatoid arthritis or systemic lupus erythematosus in a case-control study of Koreans. Arthritis Rheum 2006; 54: 3838–3841.

    CAS  Google Scholar 

  91. Sanchez E, Callejas JL, Sabio JM, de Haro M, Camps M, de Ramon E et al. Polymorphisms of the FCRL3 gene in a Spanish population of systemic lupus erythematosus patients. Rheumatology (Oxford) 2006; 45: 1044–1046.

    CAS  Google Scholar 

  92. Oliver FJ, Menissier-de Murcia J, de Murcia G . Poly(ADP-ribose) polymerase in the cellular response to DNA damage, apoptosis, and disease. Am J Hum Genet 1999; 64: 1282–1288.

    CAS  Google Scholar 

  93. Tsao BP, Cantor RM, Grossman JM, Shen N, Teophilov NT, Wallace DJ et al. PARP alleles within the linked chromosomal region are associated with systemic lupus erythematosus. J Clin Invest 1999; 103: 1135–1140.

    CAS  Google Scholar 

  94. Delrieu O, Michel M, Frances C, Meyer O, Michel C, Wittke F et al. Poly(ADP-ribose) polymerase alleles in French Caucasians are associated neither with lupus nor with primary antiphospholipid syndrome. GRAID Research Group. Group for Research on Auto-Immune Disorders. Arthritis Rheum 1999; 42: 2194–2197.

    CAS  Google Scholar 

  95. Hur JW, Sung YK, Shin HD, Park BL, Cheong HS, Bae SC . Poly(ADP-ribose) polymerase (PARP) polymorphisms associated with nephritis and arthritis in systemic lupus erythematosus. Rheumatology (Oxford) 2006; 45: 711–717.

    CAS  Google Scholar 

  96. Chen JY, Wang CM, Lu SC, Chou YH, Luo SF . Association of apoptosis-related microsatellite polymorphisms on chromosome 1q in Taiwanese systemic lupus erythematosus patients. Clin Exp Immunol 2006; 143: 281–287.

    CAS  Google Scholar 

  97. Nishimura H, Honjo T . PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends Immunol 2001; 22: 265–268.

    CAS  Google Scholar 

  98. Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet 2002; 32: 666–669.

    CAS  Google Scholar 

  99. Prokunina L, Gunnarsson I, Sturfelt G, Truedsson L, Seligman VA, Olson JL et al. The systemic lupus erythematosus-associated PDCD1 polymorphism PD1.3A in lupus nephritis. Arthritis Rheum 2004; 50: 327–328.

    CAS  Google Scholar 

  100. Ferreiros-Vidal I, Gomez-Reino JJ, Barros F, Carracedo A, Carreira P, Gonzalez-Escribano F et al. Association of PDCD1 with susceptibility to systemic lupus erythematosus: evidence of population-specific effects. Arthritis Rheum 2004; 50: 2590–2597.

    CAS  Google Scholar 

  101. Johansson M, Arlestig L, Moller B, Rantapaa-Dahlqvist S . Association of a PDCD1 polymorphism with renal manifestations in systemic lupus erythematosus. Arthritis Rheum 2005; 52: 1665–1669.

    CAS  Google Scholar 

  102. Nielsen C, Laustrup H, Voss A, Junker P, Husby S, Lillevang ST . A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients. Lupus 2004; 13: 510–516.

    CAS  Google Scholar 

  103. Sanghera DK, Manzi S, Bontempo F, Nestlerode C, Kamboh MI . Role of an intronic polymorphism in the PDCD1 gene with the risk of sporadic systemic lupus erythematosus and the occurrence of antiphospholipid antibodies. Hum Genet 2004; 115: 393–398.

    CAS  Google Scholar 

  104. Lin SC, Yen JH, Tsai JJ, Tsai WC, Ou TT, Liu HW et al. Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus. Arthritis Rheum 2004; 50: 770–775.

    CAS  Google Scholar 

  105. Wang SC, Chen YJ, Ou TT, Wu CC, Tsai WC, Liu HW et al. Programmed death-1 gene polymorphisms in patients with systemic lupus erythematosus in Taiwan. J Clin Immunol 2006; 26: 506–511.

    Google Scholar 

  106. Liang D, Huang XQ, Shen N, Mao HQ, Feng XB, Huang XF et al. Variations within OLF1/EBF-associated zinc finger protein gene confer susceptibility to lupus nephritis in Chinese population]. Zhonghua Yi Xue Za Zhi 2005; 85: 949–954.

    CAS  Google Scholar 

  107. Cunninghame Graham DS, Manku H, Wagner S, Reid J, Timms K, Gutin A et al. Association of IRF5 in UK SLE families identifies a variant involved in polyadenylation. Hum Mol Genet 2007; 16: 579–591.

    CAS  Google Scholar 

  108. Demirci FY, Manzi S, Ramsey-Goldman R, Minster RL, Kenney M, Shaw PS et al. Association of a common interferon regulatory factor 5 (IRF5) variant with increased risk of systemic lupus erythematosus (SLE). Ann Hum Genet 2007; 71 (Part 3): 308–311.

    CAS  Google Scholar 

  109. Ferreiro-Neira I, Calaza M, Alonso-Perez E, Marchini M, Scorza R, Sebastiani GD et al. Opposed independent effects and epistasis in the complex association of IRF5 to SLE. Genes Immun 2007; 8: 429–438.

    CAS  Google Scholar 

  110. Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW et al. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 2006; 38: 550–555.

    CAS  Google Scholar 

  111. Reddy MV, Velazquez-Cruz R, Baca V, Lima G, Granados J, Orozco L et al. Genetic association of IRF5 with SLE in Mexicans: higher frequency of the risk haplotype and its homozygozity than Europeans. Hum Genet 2007; 121: 721–727.

    Google Scholar 

  112. Sigurdsson S, Nordmark G, Goring HH, Lindroos K, Wiman AC, Sturfelt G et al. Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J Hum Genet 2005; 76: 528–537.

    CAS  Google Scholar 

  113. Graham RR, Kyogoku C, Sigurdsson S, Vlasova IA, Davies LR, Baechler EC et al. Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc Natl Acad Sci USA 2007; 104: 6758–6763.

    CAS  Google Scholar 

  114. Sigurdsson S, Goring HH, Kristjansdottir G, Milani L, Nordmark G, Sandling JK et al. Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for systemic lupus erythematosus. Hum Mol Genet 2008; 17: 872–881.

    CAS  Google Scholar 

  115. Niewold TB, Kelly JA, Flesch MH, Espinoza LR, Harley JB, Crow MK . Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Arthritis Rheum 2008; 58: 2481–2487.

    CAS  Google Scholar 

  116. Shin HD, Sung YK, Choi CB, Lee SO, Lee HW, Bae SC . Replication of the genetic effects of IFN regulatory factor 5 (IRF5) on systemic lupus erythematosus in a Korean population. Arthritis Res Ther 2007; 9: R32.

    Google Scholar 

  117. Kawasaki A, Kyogoku C, Ohashi J, Miyashita R, Hikami K, Kusaoi M et al. Association of IRF5 polymorphisms with systemic lupus erythematosus in a Japanese population: support for a crucial role of intron 1 polymorphisms. Arthritis Rheum 2008; 58: 826–834.

    CAS  Google Scholar 

  118. Siu HO, Yang W, Lau CS, Chan TM, Wong RW, Wong WH et al. Association of a haplotype of IRF5 gene with systemic lupus erythematosus in Chinese. J Rheumatol 2008; 35: 360–362.

    CAS  Google Scholar 

  119. Shin HD, Kim I, Choi CB, Lee SO, Lee HW, Bae SC . Different genetic effects of interferon regulatory factor 5 (IRF5) polymorphisms on systemic lupus erythematosus in a Korean population. J Rheumatol 2008; 35: 2148–2151.

    CAS  Google Scholar 

  120. Watford WT, Hissong BD, Bream JH, Kanno Y, Muul L, O'Shea JJ . Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Immunol Rev 2004; 202: 139–156.

    CAS  Google Scholar 

  121. Morinobu A, Gadina M, Strober W, Visconti R, Fornace A, Montagna C et al. STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation. Proc Natl Acad Sci USA 2002; 99: 12281–12286.

    CAS  Google Scholar 

  122. Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW et al. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 2007; 357: 977–986.

    CAS  Google Scholar 

  123. Harley JB, Alarcon-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, Moser KL et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 2008; 40: 204–210.

    CAS  Google Scholar 

  124. Hom G, Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S et al. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 2008; 358: 900–909.

    CAS  Google Scholar 

  125. Kobayashi S, Ikari K, Kaneko H, Kochi Y, Yamamoto K, Shimane K et al. Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population. Arthritis Rheum 2008; 58: 1940–1946.

    Google Scholar 

  126. Namjou B, Sestak AL, Amstrong DL, Zidovetzki R, Kelly JA, Jacob N et al. High density genotyping of STAT4 gene reveals multiple haplotypic associations with systemic lupus erythematosus in different racial group. Arthritis Rheum (in press).

  127. Cloutier JF, Veillette A . Association of inhibitory tyrosine protein kinase p50csk with protein tyrosine phosphatase PEP in T cells and other hemopoietic cells. EMBO J 1996; 15: 4909–4918.

    CAS  Google Scholar 

  128. Kaufman KM, Kelly JA, Herring BJ, Adler AJ, Glenn SB, Namjou B et al. Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus. Arthritis Rheum 2006; 54: 2533–2540.

    CAS  Google Scholar 

  129. Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE et al. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet 2004; 75: 504–507.

    CAS  Google Scholar 

  130. Baca V, Velazquez-Cruz R, Salas-Martinez G, Espinosa-Rosales F, Saldana-Alvarez Y, Orozco L . Association analysis of the PTPN22 gene in childhood-onset systemic lupus erythematosus in Mexican population. Genes Immun 2006; 7: 693–695.

    CAS  Google Scholar 

  131. Viken MK, Amundsen SS, Kvien TK, Boberg KM, Gilboe IM, Lilleby V et al. Association analysis of the 1858C>T polymorphism in the PTPN22 gene in juvenile idiopathic arthritis and other autoimmune diseases. Genes Immun 2005; 6: 271–273.

    CAS  Google Scholar 

  132. Carlton VE, Hu X, Chokkalingam AP, Schrodi SJ, Brandon R, Alexander HC et al. PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis. Am J Hum Genet 2005; 77: 567–581.

    CAS  Google Scholar 

  133. Ikari K, Momohara S, Inoue E, Tomatsu T, Hara M, Yamanaka H et al. Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population. Rheumatology (Oxford) 2006; 45: 1345–1348.

    CAS  Google Scholar 

  134. Lee HS, Korman BD, Le JM, Kastner DL, Remmers EF, Gregersen PK et al. Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations. Arthritis Rheum 2009; 60: 364–371.

    CAS  Google Scholar 

  135. Jones PA, Takai D . The role of DNA methylation in mammalian epigenetics. Science 2001; 293: 1068–1070.

    CAS  Google Scholar 

  136. Attwood JT, Yung RL, Richardson BC . DNA methylation and the regulation of gene transcription. Cell Mol Life Sci 2002; 59: 241–257.

    CAS  Google Scholar 

  137. Park BL, Kim LH, Shin HD, Park YW, Uhm WS, Bae SC . Association analyses of DNA methyltransferase-1 (DNMT1) polymorphisms with systemic lupus erythematosus. J Hum Genet 2004; 49: 642–646.

    CAS  Google Scholar 

  138. Sawalha AH, Webb R, Han S, Kelly JA, Kaufman KM, Kimberly RP et al. Common variants within MECP2 confer risk of systemic lupus erythematosus. PLoS ONE 2008; 3: e1727.

    Google Scholar 

  139. Sallai K, Nagy E, Derfalvy B, Muzes G, Gergely P . Antinucleosome antibodies and decreased deoxyribonuclease activity in sera of patients with systemic lupus erythematosus. Clin Diagn Lab Immunol 2005; 12: 56–59.

    CAS  Google Scholar 

  140. Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M et al. Mutation of DNASE1 in people with systemic lupus erythematosus. Nat Genet 2001; 28: 313–314.

    CAS  Google Scholar 

  141. Simmonds MJ, Heward JM, Kelly MA, Allahabadia A, Foxall H, Gordon C et al. A nonsense mutation in exon 2 of the DNase I gene is not present in UK subjects with systemic lupus erythematosus and Graves' disease: comment on the article by Rood et al. Arthritis Rheum 2002; 46: 3109–3110.

    Google Scholar 

  142. Chakraborty P, Hadj Kacem H, Makni-Karray K, Jarraya F, Hachicha J, Ayadi H . The A/T mutation in exon 2 of the DNASE1 gene is not present in Tunisian patients with systemic lupus erythematosus or in healthy subjects. Arthritis Rheum 2003; 48: 3297–3298.

    CAS  Google Scholar 

  143. Shin HD, Park BL, Kim LH, Lee HS, Kim TY, Bae SC . Common DNase I polymorphism associated with autoantibody production among systemic lupus erythematosus patients. Hum Mol Genet 2004; 13: 2343–2350.

    CAS  Google Scholar 

  144. Feng XB, Shen N, Qian J, Sun L, Hua J, Chen SL . Single nucleotide polymorphisms of deoxyribonuclease I and their expression in Chinese systemic lupus erythematosus patients. Chin Med J (Engl) 2004; 117: 1670–1676.

    CAS  Google Scholar 

  145. Bodano A, Gonzalez A, Ferreiros-Vidal I, Balada E, Ordi J, Carreira P et al. Association of a non-synonymous single-nucleotide polymorphism of DNASEI with SLE susceptibility. Rheumatology (Oxford) 2006; 45: 819–823.

    CAS  Google Scholar 

  146. Bodano A, Gonzalez A, Balada E, Ordi J, Carreira P, Gomez-Reino JJ et al. Study of DNASE I gene polymorphisms in systemic lupus erythematosus susceptibility. Ann Rheum Dis 2007; 66: 560–561.

    CAS  Google Scholar 

  147. Shin HD, Park BL, Cheong HS, Lee HS, Jun JB, Bae SC . DNase II polymorphisms associated with risk of renal disorder among systemic lupus erythematosus patients. J Hum Genet 2005; 50: 107–111.

    CAS  Google Scholar 

  148. Hur JW, Sung YK, Shin HD, Park BL, Cheong HS, Bae SC . TREX1 polymorphisms associated with autoantibodies in patients with systemic lupus erythematosus. Rheumatol Int 2008; 28: 783–789.

    CAS  Google Scholar 

  149. Kim I, Hur NW, Shin HD, Park BL, Cheong HS, Bae SC . Associations of DNase IV polymorphisms with autoantibodies in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2008; 47: 996–999.

    CAS  Google Scholar 

  150. Greenwald RJ, Latchman YE, Sharpe AH . Negative co-receptors on lymphocytes. Curr Opin Immunol 2002; 14: 391–396.

    CAS  Google Scholar 

  151. Heward JM, Allahabadia A, Carr-Smith J, Daykin J, Cockram CS, Gordon C et al. No evidence for allelic association of a human CTLA-4 promoter polymorphism with autoimmune thyroid disease in either population-based case-control or family-based studies. Clin Endocrinol (Oxf) 1998; 49: 331–334.

    CAS  Google Scholar 

  152. Heward J, Gordon C, Allahabadia A, Barnett AH, Franklyn JA, Gough SC . The A-G polymorphism in exon 1 of the CTLA-4 gene is not associated with systemic lupus erythematosus. Ann Rheum Dis 1999; 58: 193–195.

    CAS  Google Scholar 

  153. Pullmann Jr R, Lukac J, Skerenova M, Rovensky J, Hybenova J, Melus V et al. Cytotoxic T lymphocyte antigen 4 (CTLA-4) dimorphism in patients with systemic lupus erythematosus. Clin Exp Rheumatol 1999; 17: 725–729.

    Google Scholar 

  154. Parks CG, Hudson LL, Cooper GS, Dooley MA, Treadwell EL, St Clair EW et al. CTLA-4 gene polymorphisms and systemic lupus erythematosus in a population-based study of whites and African-Americans in the southeastern United States. Lupus 2004; 13: 784–791.

    CAS  Google Scholar 

  155. Aguilar F, Torres B, Sanchez-Roman J, Nunez-Roldan A, Gonzalez-Escribano MF . CTLA4 polymorphism in Spanish patients with systemic lupus erythematosus. Hum Immunol 2003; 64: 936–940.

    CAS  Google Scholar 

  156. Fernandez-Blanco L, Perez-Pampin E, Gomez-Reino JJ, Gonzalez A . A CTLA-4 polymorphism associated with susceptibility to systemic lupus erythematosus. Arthritis Rheum 2004; 50: 328–329.

    CAS  Google Scholar 

  157. Lee YH, Kim YR, Ji JD, Sohn J, Song GG . Polymorphisms of the CTLA-4 exon 1 and promoter gene in systemic lupus erythematosus. Lupus 2001; 10: 601–605.

    CAS  Google Scholar 

  158. Hudson LL, Rocca K, Song YW, Pandey JP . CTLA-4 gene polymorphisms in systemic lupus erythematosus: a highly significant association with a determinant in the promoter region. Hum Genet 2002; 111: 452–455.

    CAS  Google Scholar 

  159. Matsushita M, Tsuchiya N, Shiota M, Komata T, Matsuta K, Zama K et al. Lack of a strong association of CTLA-4 exon 1 polymorphism with the susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese: an association study using a novel variation screening method. Tissue Antigens 1999; 54: 578–584.

    CAS  Google Scholar 

  160. Ahmed S, Ihara K, Kanemitsu S, Nakashima H, Otsuka T, Tsuzaka K et al. Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population. Rheumatology (Oxford) 2001; 40: 662–667.

    CAS  Google Scholar 

  161. Takeuchi F, Kuwata S, Mori M . CTLA-4 −1661A/G and −1772T/C dimorphisms in Japanese patients with systemic lupus erythematosus. J Rheumatol 2005; 32: 2062.

    Google Scholar 

  162. Liu MF, Wang CR, Lin LC, Wu CR . CTLA-4 gene polymorphism in promoter and exon-1 regions in Chinese patients with systemic lupus erythematosus. Lupus 2001; 10: 647–649.

    CAS  Google Scholar 

  163. Xu AP, Yin PD, Su XY . [Association of CTLA-4 promoter −1722 polymorphism with systemic lupus erythematosus in Chinese]. Di Yi Jun Yi Da Xue Xue Bao 2004; 24: 1107–1112.

    CAS  Google Scholar 

  164. Lee YH, Harley JB, Nath SK . CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis. Hum Genet 2005; 116: 361–367.

    CAS  Google Scholar 

  165. Garred P, Madsen HO, Halberg P, Petersen J, Kronborg G, Svejgaard A et al. Mannose-binding lectin polymorphisms and susceptibility to infection in systemic lupus erythematosus. Arthritis Rheum 1999; 42: 2145–2152.

    CAS  Google Scholar 

  166. Sullivan KE, Jawad AF, Piliero LM, Kim N, Luan X, Goldman D et al. Analysis of polymorphisms affecting immune complex handling in systemic lupus erythematosus. Rheumatology (Oxford) 2003; 42: 446–452.

    CAS  Google Scholar 

  167. Bertoli AM, Fernandez M, McGwin Jr G, Alarcon GS, Tan FK, Reveille JD et al. Systemic lupus erythematosus in a multiethnic US cohort: XXXVI. Influence of mannose-binding lectin exon 1 polymorphisms in disease manifestations, course, and outcome. Arthritis Rheum 2006; 54: 1703–1704.

    CAS  Google Scholar 

  168. Ohlenschlaeger T, Garred P, Madsen HO, Jacobsen S . Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med 2004; 351: 260–267.

    CAS  Google Scholar 

  169. Lee YH, Witte T, Momot T, Schmidt RE, Kaufman KM, Harley JB et al. The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: two case-control studies and a meta-analysis. Arthritis Rheum 2005; 52: 3966–3974.

    CAS  Google Scholar 

  170. Jakab L, Laki J, Sallai K, Temesszentandrasi G, Pozsonyi T, Kalabay L et al. Association between early onset and organ manifestations of systemic lupus erythematosus (SLE) and a down-regulating promoter polymorphism in the MBL2 gene. Clin Immunol 2007; 125: 230–236.

    CAS  Google Scholar 

  171. Villarreal J, Crosdale D, Ollier W, Hajeer A, Thomson W, Ordi J et al. Mannose binding lectin and FcgammaRIIa (CD32) polymorphism in Spanish systemic lupus erythematosus patients. Rheumatology (Oxford) 2001; 40: 1009–1012.

    CAS  Google Scholar 

  172. Horiuchi T, Tsukamoto H, Morita C, Sawabe T, Harashima S, Nakashima H et al. Mannose binding lectin (MBL) gene mutation is not a risk factor for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Japanese. Genes Immun 2000; 1: 464–466.

    CAS  Google Scholar 

  173. Tsutsumi A, Sasaki K, Wakamiya N, Ichikawa K, Atsumi T, Ohtani K et al. Mannose-binding lectin gene: polymorphisms in Japanese patients with systemic lupus erythematosus, rheumatoid arthritis and Sjogren's syndrome. Genes Immun 2001; 2: 99–104.

    CAS  Google Scholar 

  174. Takahashi R, Tsutsumi A, Ohtani K, Muraki Y, Goto D, Matsumoto I et al. Association of mannose binding lectin (MBL) gene polymorphism and serum MBL concentration with characteristics and progression of systemic lupus erythematosus. Ann Rheum Dis 2005; 64: 311–314.

    CAS  Google Scholar 

  175. Ip WK, Chan SY, Lau CS, Lau YL . Association of systemic lupus erythematosus with promoter polymorphisms of the mannose-binding lectin gene. Arthritis Rheum 1998; 41: 1663–1668.

    CAS  Google Scholar 

  176. Li SG, Huang F, Liu XY, Deng XX, Xu M, Cong XZ et al. [The role of mannose binding lectin in the pathogenesis of systemic lupus erythematosus]. Zhonghua Yi Xue Za Zhi 2006; 86: 463–467.

    CAS  Google Scholar 

  177. Tesch GH, Maifert S, Schwarting A, Rollins BJ, Kelley VR . Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice. J Exp Med 1999; 190: 1813–1824.

    CAS  Google Scholar 

  178. Brown KS, Nackos E, Morthala S, Jensen LE, Whitehead AS, Von Feldt JM . Monocyte chemoattractant protein-1: plasma concentrations and A(−2518)G promoter polymorphism of its gene in systemic lupus erythematosus. J Rheumatol 2007; 34: 740–746.

    CAS  Google Scholar 

  179. Tucci M, Barnes EV, Sobel ES, Croker BP, Segal MS, Reeves WH et al. Strong association of a functional polymorphism in the monocyte chemoattractant protein 1 promoter gene with lupus nephritis. Arthritis Rheum 2004; 50: 1842–1849.

    CAS  Google Scholar 

  180. Lima G, Soto-Vega E, Atisha-Fregoso Y, Sanchez-Guerrero J, Vallejo M, Vargas-Alarcon G et al. MCP-1, RANTES, and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus. Hum Immunol 2007; 68: 980–985.

    CAS  Google Scholar 

  181. Aguilar F, Gonzalez-Escribano MF, Sanchez-Roman J, Nunez-Roldan A . MCP-1 promoter polymorphism in Spanish patients with systemic lupus erythematosus. Tissue Antigens 2001; 58: 335–338.

    CAS  Google Scholar 

  182. Sanchez E, Sabio JM, Callejas JL, de Ramon E, Garcia-Portales R, Garcia-Hernandez FJ et al. Association study of genetic variants of pro-inflammatory chemokine and cytokine genes in systemic lupus erythematosus. BMC Med Genet 2006; 7: 48.

    Google Scholar 

  183. Hwang SY, Cho ML, Park B, Kim JY, Kim YH, Min DJ et al. Allelic frequency of the MCP-1 promoter −2518 polymorphism in the Korean population and in Korean patients with rheumatoid arthritis, systemic lupus erythematosus and adult-onset Still's disease. Eur J Immunogenet 2002; 29: 413–416.

    CAS  Google Scholar 

  184. Kim HL, Lee DS, Yang SH, Lim CS, Chung JH, Kim S et al. The polymorphism of monocyte chemoattractant protein-1 is associated with the renal disease of SLE. Am J Kidney Dis 2002; 40: 1146–1152.

    CAS  Google Scholar 

  185. Nakashima H, Akahoshi M, Shimizu S, Inoue Y, Miyake K, Ninomiya I et al. Absence of association between the MCP-1 gene polymorphism and histological phenotype of lupus nephritis. Lupus 2004; 13: 165–167.

    CAS  Google Scholar 

  186. Ye DQ, Hu YS, Li XP, Yang SG, Hao JH, Huang F et al. The correlation between monocyte chemoattractant protein-1 and the arthritis of systemic lupus erythematosus among Chinese. Arch Dermatol Res 2005; 296: 366–371.

    CAS  Google Scholar 

  187. Liao CH, Yao TC, Chung HT, See LC, Kuo ML, Huang JL . Polymorphisms in the promoter region of RANTES and the regulatory region of monocyte chemoattractant protein-1 among Chinese children with systemic lupus erythematosus. J Rheumatol 2004; 31: 2062–2067.

    CAS  Google Scholar 

  188. Aoki Y, Kim YT, Stillwell R, Kim TJ, Pillai S . The SH2 domains of Src family kinases associate with Syk. J Biol Chem 1995; 270: 15658–15663.

    CAS  Google Scholar 

  189. Yokoyama K, Su Ih IH, Tezuka T, Yasuda T, Mikoshiba K, Tarakhovsky A et al. BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP(3) receptor. EMBO J 2002; 21: 83–92.

    CAS  Google Scholar 

  190. Kozyrev SV, Abelson AK, Wojcik J, Zaghlool A, Linga Reddy MV, Sanchez E et al. Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nat Genet 2008; 40: 211–216.

    CAS  Google Scholar 

  191. Buyon JP, Shadick N, Berkman R, Hopkins P, Dalton J, Weissmann G et al. Surface expression of Gp 165/95, the complement receptor CR3, as a marker of disease activity in systemic Lupus erythematosus. Clin Immunol Immunopathol 1988; 46: 141–149.

    CAS  Google Scholar 

  192. Witte T, Dumoulin FL, Gessner JE, Schubert J, Gotze O, Neumann C et al. Defect of a complement receptor 3 epitope in a patient with systemic lupus erythematosus. J Clin Invest 1993; 92: 1181–1187.

    CAS  Google Scholar 

  193. Nath SK, Han S, Kim-Howard X, Kelly JA, Viswanathan P, Gilkeson GS et al. A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet 2008; 40: 152–154.

    CAS  Google Scholar 

  194. Han S, Kim-Howard X, Deshmukh H, Kamatani Y, Viswanathan P, Guthridge JM et al. Evaluation of imputation-based association in and around the integrin-alpha-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE). Hum Mol Genet 2009; 18: 1171–1180.

    CAS  Google Scholar 

  195. Zou X, Qiu G, Chen C, Wu M, Hu Y, Zheng H et al. Expression pattern and subcellular localization of five splice isoforms of human PXK. Int J Mol Med 2005; 16: 701–707.

    CAS  Google Scholar 

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Acknowledgements

This study was supported by a grant of the Korea Healthcare technology R&D project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (no. A010252 and A080588) and the Research Program for New Drug Target Discovery (no. M10748000231-08N4800-23110 to C Kang).

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  1. Department of Rheumatology, The Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea

    I Kim, Y J Kim, C-B Choi, Y-K Sung, H-S Lee & S-C Bae

  2. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea

    K Kim & C Kang

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Kim, I., Kim, Y., Kim, K. et al. Genetic studies of systemic lupus erythematosus in Asia: where are we now?. Genes Immun 10, 421–432 (2009). https://doi.org/10.1038/gene.2009.24

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