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December 2002, Volume 3, Number 8, Pages 488-493
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Studies on the association of Fcbold gamma receptor IIA, IIB, IIIA and IIIB polymorphisms with rheumatoid arthritis in the Japanese: evidence for a genetic interaction between HLA-DRB1 and FCGR3A
C Kyogoku1, N Tsuchiya1, K Matsuta2 and K Tokunaga1

1Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

2Matsuta Clinic, Tokyo, Japan

Correspondence to: Dr N Tsuchiya, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. E-mail: tsuchiya-tky@umin.ac.jp

Supported by the Grant-in-Aid for Scientific Research on Priority Areas (C) 'Medical Genome Science', the Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Science, Sports and Culture of Japan, Health Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan, and the Grant-in-Aid for JSPS Fellows.

Abstract

We recently detected a new single nucleotide polymorphism of Fcbold gammaRIIB 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=0.009, Pcorr=0.07). In conclusion, FCGR3A-176F/F genotype was considered to confer risk through genetic interaction with HLA-DRB1 SE.

Genes and Immunity (2002) 3,488-493. doi:10.1038/sj.gene.6363921

Keywords

Fcgamma receptor; FCGR3A polymorphism; rheumatoid arthritis; HLA-DRB1 shared epitope

Received 14 May 2002; revised 8 July 2002; accepted 9 July 2002
December 2002, Volume 3, Number 8, Pages 488-493
Table of contents    Previous  Abstract  Next   Full text  PDF
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