Studies on the association of Fcγ receptor IIA, IIB, IIIA and IIIB polymorphisms with rheumatoid arthritis in the Japanese: evidence for a genetic interaction between HLA-DRB1 and FCGR3A

Abstract

We recently detected a new single nucleotide polymorphism of FcgRIIB gene, which alters an amino acid within the transmembrane domain from Ile to Thr (I232T), and its association with SLE in the Japanese. This study was performed to examine whether FCGR2B-I232T was associated with susceptibility to rheumatoid arthritis in the Japanese. At the same time, FCGR2A, 3A and 3B polymorphisms were also examined. Genotyping of FCGR2B-I232T, FCGR2A-H131R, FCGR3A-F176V and FCGR3B-NA1/2 polymorphisms were performed using genomic DNA. Association with RA was analyzed in 382 Japanese patients with RA and 303 healthy individuals using a case-control approach. In addition, the same groups of patients and controls were genotyped for HLA-DRB1 to examine possible interaction with FCGR genes. Significantly different distribution of genotype, allele carrier and allele frequencies was not observed between patients with RA and healthy individuals in any of the four polymorphisms. When the subjects were stratified according to the carriage of HLA-DRB1 shared epitope (SE), significant increase of FCGR3A-176F/F genotype was observed in SE positive patients compared with SE positive healthy individuals (P ¼ 0.009, P corr ¼ 0.07). In conclusion, FCGR3A-176F/F genotype was considered to confer risk through genetic interaction with HLA-DRB1 SE.

Utilization of Immunoglobulin G Fc Receptors by Human Immunodeficiency Virus Type 1: a Specific Role for Antibodies against the Membrane-Proximal External Region of gp41

“…83,2009 UTILIZATION OF Fc␥R BY HIV-1 gp41 MPER ANTIBODIES 7407 this receptor (23,100). In the present study, the separate cell lines expressed the H form of Fc␥RIIa and the F form of Fc␥RIIIa as being more prevalent in humans (56,59,92,101). In summary, Fc␥RI and Fc␥RIIb augmented the neutralizing activities of HIV-1 gp41 MPER-specific Abs by a mechanism that was highly dependent on the epitope and moderately dependent on the IgG subclass of the Ab.…”

FcγRIIa Genotype Predicts Progression of HIV Infection

“…Genotype frequencies are fairly similar throughout the world with VV found in ϳ10 -20% and FV and FF each occurring in ϳ45% of the population (23,26,28). IgG1 and IgG3 bind with higher affinity to the V form of the receptor than to the F form (22,29).…”

“…Outside of Asia, the HH and RR genotypes each occur in ϳ25% of the population, and the RH genotype occurs in ϳ50% (23,24). There is marked skewing of this distribution in East Asia, where 50 -60% of individuals are H homozygotes and Ͻ10% carry the RR genotype (23,25,26).…”

Copy number variation of Fc gamma receptor genes and disease predisposition

“…Similarly, a functional polymorphism in FCGR3A results in an amino acid substitution at position 158 of phenylalanine for valine which reduces the affinity of IgG1, IgG3 and IgG4 binding to the receptor. These variants, which may lead to a reduced clearance of immune complexes, have been shown in previous studies to contribute to the pathogenesis of autoimmune disorders (Kyogoku et al, 2002).…”