Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases

Mamtani, Manju; Anaya, Juan Manuel; He, Weijing; Ahuja, Sunil K.

doi:10.1038/gene.2009.71

Cited by 78 publications

(88 citation statements)

References 39 publications

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“…This is the first report in SSc and is consistent with the association reported for SLE, where published ORs range from 1.47 to 1.65. [7][8][9][10][11][12][13] Although the P value is modest (0.007), this likely represents genuine association given the prior evidence supporting a role for FCGR3B deletion in SSc. Membranebound FcgR3B is involved in the adherence of neutrophils to endothelial cells at sites of infection as well as in IC uptake.…”

Section: Discussionmentioning

confidence: 84%

“…14 ) The FCGR3B CN allele distribution among the controls (CNo2 ¼ 7.6%, CN 2 ¼ 82.6% and CN42 ¼ 9.8%) is similar to that observed in other healthy Caucasian populations as determined by multiplex ligand-dependent probe amplification or paralog ratio testing (CNo2 ¼ 6.7-7.8%, CN 2 ¼ 81.1-82.2% and CN42 ¼ 9.4-11.8%). 8,12,13,15,16 The influence of possessing o2 copies of FCGR3B on SSc risk was tested under the hypothesis that any association of FCGR3B with disease would be similar to that evident in SLE, where CNo2 is a risk factor. [5][6][7][8][9][10] There was significant evidence that possessing fewer than two copies of FCGR3B is a risk factor for SSc (odds ratio (OR) ¼ 1.55 (1.13-2.14), P ¼ 0.007) ( We tested for association between FCGR3B CNo2 and limited cutaneous or diffuse cutaneous SSc, and the presence or absence of anti-topoisomerase I and anti-centromere antibodies.…”

Section: Resultsmentioning

confidence: 99%

“…6,7 In particular, CNo2 has been reported to be a risk factor for SLE in a number of studies. [7][8][9][10][11][12][13] Given the evidence for shared genetic susceptibility between SSc and SLE, we hypothesised that copy-number variation in FCGR3B has a role in the pathology of SSc. In order to evaluate this hypothesis, we tested for association between FCGR3B gene dosage and SSc in a Caucasian case-control sample set under the specific hypothesis that deletion of FCGR3B is a risk factor in comparison with diploid and increased CN.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of p1 was a significant risk factor for SSc (OR ¼ 1.55 (1.13-2.14), P ¼ 0.007) relative to CNX2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.

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Section: Discussionmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…Polymerase chain reaction (PCR) analyses of rs447536 and rs448740 have shown good accordance with serotype 13,14 . Regarding FCGR3B copy number, pSS was associated with deletion in a recent study on 174 pSS patients and 162 controls 15 , and both deletion and duplication were associated with the disease in a study with a small pSS cohort 16 . The aim of the present study was to explore whether any of the mentioned FcR gene SNPs were associated with pSS in a larger case-control association study, and to possibly replicate previous findings concerning FCGR3B copy number variation (CNV).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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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.

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“…A CNV caused by genomic rearrangements such as deletions, duplications, inversions, and translocations may contribute to alteration of gene expression and subsequent phenotypic variation, which results in susceptibility or resistance to disease [9][10][11] . CNV has also been associated with autism [12][13][14][15] , schizophrenia [16][17][18][19] , cancer [20][21][22][23][24][25] , and autoimmune disease 11,[26][27][28][29][30] . Fc gamma receptor IIIb (FCGR3B), the CD16 cell surface immunoglobulin receptor, located on chromosome 1q23, is a low-affinity IgG receptor that binds with IgG complexes at the Fc region 31 .…”

Section: Introductionmentioning

confidence: 99%

Association of copy number variation in Fc gamma receptor IIIb gene with risk of Graves' ophthalmopathy

Liao¹,

Liu²,

Wan³

et al. 2012

ScienceAsia

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The functional polymorphism that explains the established association of Fc gamma receptor IIIb (FCGR3B) with Graves' disease (GD) and Graves' ophthalmopathy (GO) remains unidentified, but copy number variation (CNV) might be relevant. The aim of this study was to determine whether CNV for FCGR3B is associated with GD and GO. Genotype analysis involved 624 GD patients, including 397 without GO (GDnonGO) and 227 with GO (GDGO), and 227 healthy controls. The relative copy number (CN) of FCGR3B was determined using a relative real-time quantitative polymerase chain reaction. Our findings indicated the distribution of the relative CN of FCGR3B significantly differed between the GDGO patients and the healthy controls (p = 0.02) but not between the total GD patients and the healthy control groups (p = 0.06). Individuals with less than 2 CN or more than 2 CN of FCGR3B were at significantly decreased risk of developing GDGO. In addition, GD patients with less than 2 copies of FCGR3B were at reduced risk for developing nodular hyperplasia and vitiligo, but at increased risk for myxedema. Our results suggest that CNV of FCGR3B is associated with the development or progression of GD in Taiwan Chinese population.

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Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases

Cited by 78 publications

References 39 publications

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

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

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

Association of copy number variation in Fc gamma receptor IIIb gene with risk of Graves' ophthalmopathy

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