The genetic background of primary Sjögren’s syndrome (pSS) is partly shared with systemic lupus erythematosus (SLE). Immunoglobulin G Fc receptors are important for clearance of immune complexes. Fcγ receptor variants and gene deletion have been found to confer SLE risk. In this study, four Fcγ receptor single-nucleotide polymorphisms (SNPs) and one copy number variation (CNV) were studied. Swedish and Norwegian pSS patients (N=527) and controls (N=528) were genotyped for the Fcγ receptor gene variant FCGR2A H131R (rs1801274) by the Illumina GoldenGate assay. FCGR3A F158V (rs396991) was analysed in 488 patients and 485 controls, FCGR3B rs447536 was analysed in 471 patients and 467 controls, and FCGR3B rs448740 was analysed in 478 cases and 455 controls, using TaqMan SNP genotyping assays. FCGR3B CNV was analysed in 124 patients and 139 controls using a TaqMan copy number assay. None of the SNPs showed any association with pSS. Also, no FCGR3B CNV association was detected. The lack of association of pSS with Fcγ receptor gene variants indicates that defective immune complex clearance may not be as important in pSS pathogenesis as in SLE, and may point to important differences between SLE and pSS.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Cobb BL, Lessard CJ, Harley JB, Moser KL . Genes and Sjögren’s syndrome. Rheum Dis Clin North Am 2008; 34: 847–868.
Bolstad AI, Wassmuth R, Haga HJ, Jonsson R . HLA markers and clinical characteristics in Caucasians with primary Sjögren's syndrome. J Rheumatol 2001; 28: 1554–1562.
Nordmark G, Kristjansdottir G, Theander E, Eriksson P, Brun JG, Wang C et al. Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjögren's syndrome. Genes Immun 2009; 10: 68–76.
Nordmark G, Kristjansdottir G, Theander E, Appel S, Eriksson P, Vasaitis L et al. Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjogren's syndrome. Genes Immun 2011; 12: 100–109.
Karassa FB, Trikalinos TA, Ioannidis JP . The role of FcγRIIA and IIIA polymorphisms in autoimmune diseases. Biomed Pharmacother 2004; 58: 286–291.
Fanciulli M, Vyse TJ, Aitman TJ . Copy number variation of Fc gamma receptor genes and disease predisposition. Cytogenet Genome Res 2008; 123: 161–168.
Hamburger MI, Moutsopoulos HM, Lawley TJ, Frank MM . Sjögren’s syndrome: a defect in reticuloendothelial system Fc-receptor-specific clearance. Ann Internal Med 1979; 91: 534–538.
O'Sullivan MM, Walker DM, Williams BD . Reticuloendothelial Fc receptor function in patients with Sjogren's syndrome. Clin Exp Immunol 1985; 61: 483–488.
Pennec YL, Gentric AH, Jouquan JR, Youinou P . Polymorphonuclear cell functions in patients with primary Sjögren's syndrome. Clin Exp Rheumatol 1988; 6: 293–296.
Miceli-Richard C, Ohresser M, Hachulla E et al. Fcg receptor IIa and IIIa polymorphisms in primary Sjögren's syndrome. (ACR Annual meeting 2007, abstract 1086). https://acr.confex.com/acr/2007/webprogram/Paper7016.html (accessed 17 November 2012).
Salmon JE, Edberg JC, Kimberly RP . Fc gamma receptor III on human neutrophils. Allelic variants have functionally distinct capacities. J Clin Invest 1990; 85: 1287–1295.
Bredius RG, Fijen CA, De Haas M, Kuijper EJ, Weening RS, Van de Winkel JG et al. Role of neutrophil Fc gamma RIIa (CD32) and Fc gamma RIIIb (CD16) polymorphic forms in phagocytosis of human IgG1- and IgG3-opsonized bacteria and erythrocytes. Immunology 1994; 83: 624–630.
Bux J, Stein EL, Santoso S, Mueller-Eckhardt C . NA gene frequencies in the German population, determined by polymerase chain reaction with sequence-specific primers. Transfusion 1995; 35: 54–57.
Hessner MJ, Curtis BR, Endean DJ, Aster RH . Determination of neutrophil antigen gene frequencies in five ethnic groups by polymerase chain reaction with sequence-specific primers. Transfusion 1996; 36: 895–899.
Nossent JC, Rischmueller M, Lester S . Low copy number of the Fc-γ receptor 3B gene FCGR3B is a risk factor for primary Sjögren's syndrome. J Rheumatol 2012; 39: 2142–2147.
Mamtani M, Anaya JM, He W, Ahuja SK . Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases. Genes Immun 2010; 11: 155–160.
Manoussakis MN, Georgopoulou C, Zintzaras E, Spyropoulou M, Staropoulou A, Skopouli FN et al. Sjögren's syndrome associated with systemic lupus erythematosus. Clinical and laboratory profiles and comparison with primary Sjögren's syndrome. Artritis Rheum 2004; 50: 882–891.
Ghebrehiwet B, Peerschke EI . Role of C1q and C1q receptors in the pathogenesis of systemic lupus erythematosus. Curr Dir Autoimmun 2004; 7: 87–97.
Nimmerjahn F . Activating and inhibitory FcγRs in autoimmune disorders. Springer Sem Immunopathol 2006; 28: 305–319.
Breunis WB, van Mirre E, Geissler J, Laddach N, Wolbink G, van der Schoot E et al. Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B. Hum Mutat 2009; 30: E640–E650.
Thabet MM, Huizinga TW, Marques RB, Stoeken-Rijsbergen G, Bakker AM, Kurreeman FA et al. Contribution of Fcγ receptor IIIA gene 158V/F polymorphism and copy number variation to the risk of ACPA positive rheumatoid arthritis. Ann Rheum Dis 2009; 68: 1775–1780.
Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S et al. Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses. Blood 2009; 113: 3716–3725.
Willcocks LC, Lyons PA, Clatworthy MR, Robinson JI, Yang W, Newland SA et al. Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake. J Exp Med 2008; 205: 1573–1582.
Bertrand G, Duprat E, Lefranc MP, Marti J, Coste J . Characterization of human FCGR3B*02 (HNA-1b, NA2) cDNAs and IMGT standardized description of FCGR3B alleles. Tissue Antigens 2004; 64: 119–131.
Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE et al. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002; 61: 554–558.
We thank Marianne Eidsheim and Dagny Ann Sandnes from the Broegelmann Research Laboratory, University of Bergen, for excellent technical assistance. Genotyping of rs1801274 was performed by the SNP&SEQ Technology Platform in Uppsala, Sweden. Isolation and storage of some of the Swedish DNA samples were performed by Region Skåne’s Competence Centre for Clinical Research, RSKC. The Malmö Diet and Cancer Study/Malmö Preventive Medicine program provided the population-based cohort from which the Malmö controls originated. The Malmö controls consisted of a population-based cohort included in the Malmö Cost-Cancer registry. The controls from Stockholm were samples from the population-based Epidemiological Investigation of Rheumatoid Arthritis (EIRA) control cohort. This work was supported by the University of Bergen; the Strategic Research Program at Helse Bergen; the Western Norway Regional Health Authority (Helse Vest) and the Broegelmann Foundation, Bergen, Norway. Also, the Swedish Research Council, the Swedish Rheumatism Foundation, King Gustaf V’s 80-year Foundation, Ragnar Söderberg Foundation and COMBINE. The SNP Technology Platform in Uppsala, Sweden, was established by funding from the Knut and Alice Wallenberg Foundation.
The authors declare no conflict of interest.
Supplementary Information accompanies this paper on Genes and Immunity website
Rights and permissions
About this article
Cite this article
Haldorsen, K., Appel, S., Le Hellard, S. et al. No association of primary Sjögren’s syndrome with Fcγ receptor gene variants. Genes Immun 14, 234–237 (2013). https://doi.org/10.1038/gene.2013.12
- Sjögren’s syndrome
- Fc gamma receptors
- single-nucleotide polymorphism
- DNA copy number variations
This article is cited by
Reply to ‘Comment on No association of primary Sjögren’s syndrome with Fcγ receptor gene variants’
Genes & Immunity (2013)
Comment on ‘No association of primary Sjögren’s syndrome with Fcγ receptor gene variants’
Genes & Immunity (2013)