The FcγRIIIA-F158 allele is a risk factor for the development of lupus nephritis: A meta-analysis

Karassa, Fotini B.; Trikalinos, Thomas A; Ioannidis, John P. A.; investigators, Fc gamma Riiia-Sle meta-analysis

doi:10.1046/j.1523-1755.2003.00873.x

Cited by 128 publications

(79 citation statements)

References 44 publications

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“…a Indicates significance at the 0.05 level. 18,19,26,32 Previous estimates of LD between FCGR3B and other FCGR genes would have been inaccurate because of the confounding effect of FCGR3B CNV. Thus, we used our current accurate estimate of FCGR3B CN state and NA1/NA2 allotype to examine LD relations between FCGR3B and other missense polymorphisms that appear to contribute to the risk of SLE potential: FCGR2A-H131R, FCGR3A-F158V and FCGR2B-I232T.…”

Section: Resultsmentioning

confidence: 99%

“…Genetic associations have been reported between SLE and functional polymorphisms at FCGR2A, FCGR2B and FCGR3A. [16][17][18][19] Also there have been studies reporting the association of two common allotypes of FCGR3B with SLE. [20][21][22] However, the interpretation of these studies is bedevilled by the confounding effect of CNV of the FCGR3B gene.…”

Section: Introductionmentioning

confidence: 99%

“…24,25 PRT is a PCR-based assay, 25,26 which uses the high sequence identity of FCGR3A and FCGR3B to give accurate CN estimates for both. PRT returns CN measurements with more precision than qPCR because of simultaneous amplification of a target and a control.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for both copy number and allelic (NA1/NA2) risk at the FCGR3B locus in systemic lupus erythematosus

et al. 2010

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The Fcc-receptor locus on chromosome 1q23 shows copy-number variation (CNV), and it has previously been shown that individuals with reduced numbers of copies of the Fcc-receptor-IIIB gene (FCGR3B) have an increased risk of developing systemic lupus erythematosus (SLE). It is not understood whether the association arises from FCGR3B (CD16b) itself, is observed because of linkage disequilibrium with actual causal alleles and/or is an effect of CNV on flanking FCGR genes. Thus, we extended this previous work by genotyping the FCGR3B alleles NA1/NA2 and re-assaying CNV using a paralogue ratio test assay in a family study (365 families). We have developed a novel case/pseudo-control approach to analyse family data, as the phase of copy number (CN) is not known in parents and cannot always be inferred in offspring. The results, obtained by fitting logistic regression models, confirm the association of low CN of FCGR3B with SLE (P¼0.04). The risk conferred by low copies (o2) was contingent on FCGR3B allotype, being greater for deletion of NA1 than the for lower-affinity NA2. The simpler model with just CN was rejected in favour of the biallelic-CN model (P¼0.03). We observed a correlation (R 2 ¼0.75, Po0.0001) between FCGR3B CNV and neutrophil expression in both healthy controls and patients with SLE. Our results suggest that one mechanism by which CNV at this locus confers disease risk is directly as a result of reduced FccRIIIb function, either because of reduced expression (related to CNV) or because of reduced affinity for its ligand (NA1/NA2 allotype).

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evidence for both copy number and allelic (NA1/NA2) risk at the FCGR3B locus in systemic lupus erythematosus

et al. 2010

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“…Three study teams did not use the preliminary criteria for the classification of APS; nevertheless, similar results were obtained when data from these study teams were excluded. Last, the association of the Fc␥RIIA-R/H131 polymorphism with APS could be explained by the existence of linkage disequilibrium between this gene and other candidate genes on chromosome 1 that may also be more directly relevant for the risk of specific disease manifestations (54). This would require the investigation of extended haplotypes (55,56) in the future.…”

Section: Discussionmentioning

confidence: 99%

Role of the Fcγ receptor IIA polymorphism in the antiphospholipid syndrome: An international meta‐analysis

Karassa¹,

Bijl²,

Davies³

et al. 2003

Arthritis & Rheumatism

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Objective. To assess the impact of the Fc␥RIIA-R/ H131 polymorphism on the risk for antiphospholipid syndrome (APS), both primary and secondary to systemic lupus erythematosus (SLE).Methods. This international meta-analysis combined data from 9 research teams. Fc␥RIIA-R/H131 genotypes were determined in 481 APS cases (206 with primary APS), 1,420 SLE controls, and 1,655 diseasefree controls. Data were combined using fixed-effects and random-effects models.Results. Compared with disease-free controls, the RR genotype was enriched in the entire group of APS cases (odds ratio [OR] 1.65, 95% confidence interval [95% CI] 1.28-2.14); this was driven mostly by patients with secondary APS (OR 1.95, 95% CI 1.45-2.63). The excess of RR homozygotes but not heterozygotes among APS patients suggested a recessive mode of inheritance, rather than the additive model seen for SLE susceptibility, where RR conferred greatest risk, and RH intermediate risk, for SLE. This probably reflected the additional influence of another opposing genetic effect of HH homozygosity on APS predisposition (OR 0.72 for RH versus HH, 95% CI 0.55-0.96). Among SLE patients, those with APS were more frequently HH homozygotes than heterozygotes (OR 0.56 for RH versus HH, 95% CI 0.39-0.81). HH homozygosity also tended to predominate in primary APS compared with secondary APS (OR 0.50 for RR versus HH, 95% CI 0.25-0.99 by fixed-effects model). There was no significant betweenstudy heterogeneity for any of these effects.Conclusion. The Fc␥RIIA-R/H131 polymorphism is an important determinant of predisposition to APS, with different influences on SLE and APS susceptibility per se.

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“…On the other hand, we failed to replicate the association of FCGR3A-176F with the presence of lupus nephritis, which was shown in the meta-analysis of FCGR3A (12). Since the number of families that included members with nephritis was small, the possibility of a false-negative result cannot be excluded.…”

Section: Concise Communications 671mentioning

confidence: 57%

Association of Fcγ receptor IIA, but not IIB and IIIA, polymorphisms with systemic lupus erythematosus: A family‐based association study in Caucasians

Kyogoku¹,

Tsuchiya²,

Wu³

et al. 2004

Arthritis & Rheumatism

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The FcγRIIIA-F158 allele is a risk factor for the development of lupus nephritis: A meta-analysis

Abstract: The Fc gamma RIIIA-V/F158 polymorphism has a significant impact on the development of lupus nephritis.

Cited by 128 publications

References 44 publications

Evidence for both copy number and allelic (NA1/NA2) risk at the FCGR3B locus in systemic lupus erythematosus

Evidence for both copy number and allelic (NA1/NA2) risk at the FCGR3B locus in systemic lupus erythematosus

Role of the Fcγ receptor IIA polymorphism in the antiphospholipid syndrome: An international meta‐analysis

Association of Fcγ receptor IIA, but not IIB and IIIA, polymorphisms with systemic lupus erythematosus: A family‐based association study in Caucasians

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