Association of variation in Fc  receptor 3B gene copy number with rheumatoid arthritis in Caucasian samples

Abstract

Objective-There is increasing evidence that variation in gene copy number (CN) influences clinical phenotype. The low-affinity Fcγ receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment to sites of inflammation and activation of polymorphonuclear neutrophils (PMNs). Given recent evidence that low FCGR3B CN is a risk factor for systemic but not organ-specific autoimmune disease and the potential importance of PMN in the pathophysiology of rheumatoid arthritis (RA), the authors hypothesised that FCGR3B gene dosage influences susceptibility to RA.Methods-FCGR3B CN was measured in 643 cases of RA and 461 controls from New Zealand (NZ), with follow-up analysis in 768 cases and 702 controls from the Netherlands and 250 cases and 211 controls from the UK. All subjects were of Caucasian ancestry.Results-Significant evidence for an association between CN <2 and RA was observed in the Dutch cohort (OR 2.01 (95% CI 1.37 to 2.94), p=3×10-4) but not in the two smaller cohorts (OR 1.45 (95% CI 0.92 to 2.26), p=0.11 and OR 1.33 (95% CI 0.58 to 3.02), p=0.50 for the NZ and UK populations, respectively). The association was evident in a meta-analysis which included a previously published Caucasian sample set (OR 1.67 (95% CI 1.28 to 2.17), p=1.2×10-4).

Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis

“…The quantitative PCR assay method we have used has been validated previously. 2 The use of an internal reference in the PCR removes variations due to amplification efficiency and experimental conditions that can occur when test and reference genes are measured in separate wells. Cases and controls were also assayed concurrently, and a-posteriori assignment of CN rather than arbitrary rounding of non-integer values was done to minimise batch effects and systematic errors.…”

“…2 The 1000 Genomes project has recently identified two SNPs at these 3 0 positions (rs115802971 and rs115130696) in individuals of Yoruban descent in which the minor allele corresponds to the FCGR3A sequence. Although an individual carrying these minor alleles would be falsely determined to have a deletion, the allele frequencies in Caucasian populations are very low, with the minor allele of these SNPs being observed in only one of the first 380 Caucasians sequenced in the 1000 Genomes project.…”

Genome-wide scan identifies a copy number variable region at 3p21.1 that influences the TLR9 expression levels in IgA nephropathy patients

“…[7][8][9][10][11][12] However, most studies have not evaluated the contribution to this complex disorder of other forms of genetic variation, such as structural variations, mainly in the form of CNVs. 15 Indeed, CNVs have recently been shown to have an important role in complex disease phenotypes as psoriasis, 30 rheumatoid arthritis 31 and systemic lupus erythematosus. 32 Similarly, a copy number polymorphism including FCGR3 leads to a predisposition to glomerulonephritis in rats and humans.…”

New Gene Profiling in Determination of Breast Cancer Recurrence and Prognosis in Iranian Women

“…Although the functional roles of these genes in the development of immune system disorders and breast cancer are well documented (Howard et al, 1998;Hannigan et al, 2001;Fan et al, 2006;Cheng et al, 2009;McKinney et al, 2010), whether or not they contribute to increased BC risk in populations of non-European descent has not been investigated. In the present study, we investigated the expression of LSP1, HRAS, SIRT3, AP2A2 and SCUBE2 in Iranian BC patients and healthy control subjects.…”

“…Hannigan et al reported that reduced chemotactic responses of LSP1 neutrophils are associated with discontinuous primary actin-rich cortexes and large abnormal membrane protrusions (Howard et al, 1998). Overexpression of LSP1 causes morphologic and motile abnormalities characteristic of the NAD 47/89 phenotype (McKinney et al, 2010).…”