No association of primary Sjögren’s syndrome with Fcγ receptor gene variants

Abstract

and keywordsThe genetic background of primary Sjögren's syndrome (pSS) is partly shared with systemic lupus erythematosus (SLE). IgG 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 Fc 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 Fc 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.

Comment on ‘No association of primary Sjögren’s syndrome with Fcγ receptor gene variants’

“…While the Haldorsen et al 1 study, which examined FCGR3B CNV in Norwegian pSS patients, was negative, two previously published studies have both reported an association between low FCGR3B copy number and pSS in American 4 and Australian 5 cohorts, and we were the authors of this latter study. Haldorsen et al 1 suggest that the discrepancy between our two studies is due to technical superiority of their study (in terms of a small difference in the stringency of the allowable standard deviation of the replicate DCq values), or the fact that our controls were not gender matched (without providing a rationale for suggesting there will be a gender difference in autosomal FCGR3B CNV genotype frequencies in the controls). However, there are more profound differences between these two studies, and we believe it is the validity of the Haldersen et al 1 study that is in doubt.…”

“…The article by Haldorsen et al 1 describes a genetic association study for primary Sjö gren's syndrome (pSS), and the FCGR gene cluster on Chr1q22. The study evaluated both genomic copy number variation (CNV) in the FCGR3B gene, and four singlenucleotide polymorphisms (SNPs) in FCGR2A, FCGR3A and FCGR3B, respectively.…”

An Update Evolving View of Copy Number Variations in Autoimmune Diseases

“…They further identified that FCGR3R CNV is a genetic susceptibility factor for pSS (Liao et al, 2015). However, Haldorsen et al (2013) showed no association of FCGR3B CNV with pSS in the Norway and Switzerland populations. To clarify, these controversial results need more studies in more populations with different ethnicities and regions.…”

Fcγ receptors: genetic variation, function, and disease

“…FCGR3B deletion has also been implicated in one of two cohorts of Wegener's granulomatosis , RA , and Sjӧgren's Syndrome ; while duplication has been implicated in a Japanese cohort of ulcerative colitis . However, inconsistencies remain and may be due to differences in assay methodology, ethnicity, and/or disease classification.…”