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Association of UBASH3A gene polymorphism and atopic dermatitis in the Chinese Han population

Genes & Immunity volume 18, pages 158–162 (2017)Cite this article

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Abstract

Genome-wide association studies have revealed a large number of genetic-risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases share susceptibility loci. Recent evidence has demonstrated that UBASH3A gene was associated with multiple autoimmune diseases. The aim of this study was to explore the association between UBASH3A single-nucleotide polymorphisms (SNPs) and atopic dermatitis (AD) in a Chinese Han population. In total, three UBASH3A SNPs (rs11203203, rs3788013 and rs1893592) were genotyped using TaqMan genotyping assays in a Chinese Han population (1012 cases and 1362 controls). Among these SNPs, we selected the SNP rs1893592 with association values of P<5 × 10−2 for AD in the TaqMan genotyping assay data for further replication in the independent Chinese replication samples (1080 cases and 1367 controls) using a Sequenom MassARRAY system. We combined the association results in two stages using meta-analysis. We found that rs1893592 in UBASH3A showed association with AD (P=1.29 × 10−3, odds ratio=1.16). These results showed that UBASH3A gene SNP is associated with susceptibility to AD. Further fine mapping and functional studies will be required to identify true causal variant in the UBASH3A gene and its exact role in the pathogenesis of AD.

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References

  1. Paternoster L, Standl M, Waage J, Baurecht H, Hotze M, Strachan DP et al. Multi-ancestry genome-wide association study of 21000 cases and 95000 controls identifies new risk loci for atopic dermatitis. Nat Genet 2015; 47: 1449–1456.

    Article  Google Scholar 

  2. Bieber T . Atopic dermatitis. N Engl J Med 2008; 358: 1483–1494.

    Article  CAS  Google Scholar 

  3. Hanifin J, Rajka G . Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 1980; 92: 44–47.

    Google Scholar 

  4. Williams H, Stewart A, von Mutius E, Cookson W, Anderson HR, et alInternational Study of A. Is eczema really on the increase worldwide? J Allergy Clin Immunol 2008; 121: 947–954 e15.

    Article  Google Scholar 

  5. Bieber T, Novak N . Pathogenesis of atopic dermatitis: new developments. Curr Allergy Asthma Rep 2009; 9: 291–294.

    Article  CAS  Google Scholar 

  6. Ellinghaus D, Baurecht H, Esparza-Gordillo J, Rodriguez E, Matanovic A, Marenholz I et al. High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat Genet 2013; 45: 808–812.

    Article  CAS  Google Scholar 

  7. van Heel DA, Franke L, Hunt KA, Gwilliam R, Zhernakova A, Inouye M et al. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat Genet 2007; 39: 827–829.

    Article  CAS  Google Scholar 

  8. Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, Thomson BP et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 2010; 42: 508–514.

    Article  CAS  Google Scholar 

  9. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 2009; 41: 703–707.

    Article  CAS  Google Scholar 

  10. Glas J, Stallhofer J, Ripke S, Wetzke M, Pfennig S, Klein W et al. Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease. Am J Gastroenterol 2009; 104: 1737–1744.

    Article  CAS  Google Scholar 

  11. Festen EA, Goyette P, Green T, Boucher G, Beauchamp C, Trynka G et al. A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn's disease and celiac disease. PLoS Genet 2011; 7: e1001283.

    Article  CAS  Google Scholar 

  12. Gregersen PK, Amos CI, Lee AT, Lu Y, Remmers EF, Kastner DL et al. REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. Nat Genet 2009; 41: 820–823.

    Article  CAS  Google Scholar 

  13. Genetic Analysis of Psoriasis C, the Wellcome Trust Case Control C Genetic Analysis of Psoriasis C, the Wellcome Trust Case Control C Strange A Genetic Analysis of Psoriasis C, the Wellcome Trust Case Control C Capon F Genetic Analysis of Psoriasis C, the Wellcome Trust Case Control C Spencer CC Genetic Analysis of Psoriasis C, the Wellcome Trust Case Control C Knight J et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 2010; 42: 985–990.

    Article  Google Scholar 

  14. Dubois PC, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A et al. Multiple common variants for celiac disease influencing immune gene expression. Nat Genet 2010; 42: 295–302.

    Article  CAS  Google Scholar 

  15. Hakonarson H, Grant SF, Bradfield JP, Marchand L, Kim CE, Glessner JT et al. A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 2007; 448: 591–594.

    Article  CAS  Google Scholar 

  16. Ellinghaus D, Ellinghaus E, Nair RP, Stuart PE, Esko T, Metspalu A et al. Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci. Am J Hum Genet 2012; 90: 636–647.

    Article  CAS  Google Scholar 

  17. Zhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, Franke L et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet 2011; 7: e1002004.

    Article  CAS  Google Scholar 

  18. Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 2008; 359: 2767–2777.

    Article  CAS  Google Scholar 

  19. Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2014; 506: 376–381.

    Article  CAS  Google Scholar 

  20. Kim K, Bang SY, Lee HS, Cho SK, Choi CB, Sung YK et al. High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci. Ann Rheum Dis 2015; 74: e13.

    Article  Google Scholar 

  21. Grant SF, Qu HQ, Bradfield JP, Marchand L, Kim CE, Glessner JT et al. Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes. Diabetes 2009; 58: 290–295.

    Article  CAS  Google Scholar 

  22. Frederiksen BN, Steck AK, Kroehl M, Lamb MM, Wong R, Rewers M et al. Evidence of stage- and age-related heterogeneity of non-HLA SNPs and risk of islet autoimmunity and type 1 diabetes: the diabetes autoimmunity study in the young. Clin Dev Immunol 2013; 2013: 417657.

    Article  Google Scholar 

  23. Plagnol V, Howson JM, Smyth DJ, Walker N, Hafler JP, Wallace C et al. Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet 2011; 7: e1002216.

    Article  CAS  Google Scholar 

  24. Liu J, Liu J, Ni J, Leng RX, Pan HF, Ye DQ . Association of UBASH3A gene polymorphisms and systemic lupus erythematosus in a Chinese population. Gene 2015; 565: 116–121.

    Article  CAS  Google Scholar 

  25. San Luis B, Sondgeroth B, Nassar N, Carpino N . Sts-2 is a phosphatase that negatively regulates zeta-associated protein (ZAP)-70 and T cell receptor signaling pathways. J Biol Chem 2011; 286: 15943–15954.

    Article  CAS  Google Scholar 

  26. Collingwood TS, Smirnova EV, Bogush M, Carpino N, Annan RS, Tsygankov AY . T-cell ubiquitin ligand affects cell death through a functional interaction with apoptosis-inducing factor, a key factor of caspase-independent apoptosis. J Biol Chem 2007; 282: 30920–30928.

    Article  CAS  Google Scholar 

  27. Carpino N, Chen Y, Nassar N, Oh HW . The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways. Mol Immunol 2009; 46: 3224–3231.

    Article  CAS  Google Scholar 

  28. Orteu CH, Rustin MH, O'Toole E, Sabin C, Salmon M, Poulter LW et al. The inhibition of cutaneous T cell apoptosis may prevent resolution of inflammation in atopic eczema. Clin Exp Immunol 2000; 122: 150–156.

    Article  CAS  Google Scholar 

  29. Werfel T, Allam JP, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol 2016; 138: 336–349.

    Article  CAS  Google Scholar 

  30. Higgins JP, Thompson SG, Deeks JJ, Altman DG . Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.

    Article  Google Scholar 

  31. Mantel N, Haenszel W . Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719–748.

    CAS  Google Scholar 

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Acknowledgements

We are most grateful to the individuals and their families for participating in this study. This study was funded by the Youth Program of the National Natural Science Foundation of China (81301353), the Youth Program of the Natural Science Fund of Anhui province (1308085QH149) and the reserve talent program of the First affiliated hospital of Anhui medical university (2014).

Author contributions

YL conceived this study and obtained financial support. YL, X-JZ and SY participated in the design and were responsible for sample selection, genotyping and project management. F-LX, BL, L-DS and HC conducted sample selection and data management, undertook recruitment, collected the phenotyping data, undertook the related data handling and calculation, managed recruitment and obtained biological samples. F-SZ, PL, performed genotyping analysis. X-DZ undertook the data processing and statistical analysis. All of the authors contributed to the final paper, with YL, X-JZ and SY having key roles.

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Authors and Affiliations

  1. Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, Anhui, China

    Y Li, H Cheng, F-L Xiao, B Liang, F-s Zhou, P Li, X-d Zheng, L-d Sun, S Yang & X-j Zhang

  2. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, Anhui, China

    Y Li, H Cheng, F-L Xiao, B Liang, F-s Zhou, P Li, X-d Zheng, L-d Sun, S Yang & X-j Zhang

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  1. Y Li
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Correspondence to Y Li.

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Li, Y., Cheng, H., Xiao, FL. et al. Association of UBASH3A gene polymorphism and atopic dermatitis in the Chinese Han population. Genes Immun 18, 158–162 (2017). https://doi.org/10.1038/gene.2017.15

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  • DOI: https://doi.org/10.1038/gene.2017.15

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