Association analysis of functional variants of the FcgRIIa and FcgRIIIa genes with type 1 diabetes, celiac disease and rheumatoid arthritis.
until further notice
SourceHuman Molecular Genetics, 16, 21, (2007), pp. 2552-2559
Article / Letter to editor
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Human Molecular Genetics
SubjectDCN 1: Perception and Action; DCN 2: Functional Neurogenomics; EBP 1: Determinants in Health and Disease; IGMD 3: Genomic disorders and inherited multi-system disorders; N4i 1: Pathogenesis and modulation of inflammation; N4i 4: Auto-immunity, transplantation and immunotherapy; NCEBP 2: Evaluation of complex medical interventions; NCMLS 1: Immunity, infection and tissue repair; NCMLS 1: Infection and autoimmunity; NCMLS 6: Genetics and epigenetic pathways of disease; UMCN 4.2: Chronic inflammation and autoimmunity; UMCN 5.1: Genetic defects of metabolism
FcgRIIa and FcgRIIIa are potent modulators of the immune system which bind (auto)antibodies and activate immune cells. The FcgRIIa*A519G and FcgRIIIa*A559C functional variants have been associated with several immune-related diseases. We studied FcgRIIa*A519G and FcgRIIIa*A559C SNPs in type 1 diabetes (T1D), celiac disease (CD) and rheumatoid arthritis (RA) patients and controls and included a meta-analysis of all recent studies of FcgRIIIa*A559C and RA. Our cohorts comprised 350 T1D, 519 CD, 639 RA patients and 1359 controls, who were genotyped for FcgRIIa*A519G and FcgRIIIa*A559C variants. Regression and expectation maximization (EM) algorithm-based haplotype analyses were used for the data analysis. We found significant differences in genotype frequencies of FcgRIIa between controls and patients with T1D (P = 0.04), CD (P = 0.000005) and RA (P = 0.04). The FcgRIIa*519GG genotype showed an increased risk for both T1D [odds ratio (OR) = 1.51; 95% confidence interval (95% CI) 1.08-2.12; P = 0.015] and CD (OR = 1.81; 95% CI 1.35-2.37; P = 0.000004), but not for RA. There was no difference in the frequency of FcgRIIIa*A559C genotypes or allelotypes between controls with T1D, CD and RA. We found that FcgRIIa and FcgRIIIa haplotype frequencies differed significantly between controls and patients with T1D (P = 0.05) and with CD (P = 0.00038) but not with RA. Our meta-analysis showed a significant 1.37(95% CI 1.14-1.66)-fold increased risk of RA for the FcgRIIIa*559CC (158VV) genotype (P = 0.001). This is the first report that the FcgRIIa*519GG genotype predisposes to T1D and CD. We confirmed that the FcgRIIIa*559CC genotype is associated with RA. If replicated, our findings would suggest FcgRIIa*519G as a common risk factor for auto-immune diseases. This may have clinical implications with regard to efficacy or safety of antibody-based immuno-modulator therapies.
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