Association of Fc gamma receptor IIIB, but not of Fc gamma receptor IIA and IIIA polymorphisms with systemic lupus erythematosus in Japanese.
Human Fc gamma receptor (Fc gamma R) genes form a clustered gene family on chromosome 1q21-24. Although the association of Fc gamma R polymorphisms with systemic lupus erythematosus (SLE) has been extensively studied, the results are often contradictory. In this study, Fc gamma RIIA-131H/R, Fc gamma RIIIA-176F/V and Fc gamma RIIIB-NA1/2 genotypes were determined in the Japanese patients with SLE (n = 81) or rheumatoid arthritis (RA, n = 115) as well as in healthy individuals (n = 217), and possible association with the disease was tested using case-control analysis. Unlike in other populations, significant difference was not observed in the frequencies of Fc gamma RIIA and Fc gamma RIIIA genotypes between patients with SLE and healthy individuals. However, significant difference was detected in the frequencies of Fc gamma RIIIB genotypes between SLE and healthy individuals (P = 0.008). The odds ratio [OR] of the Fc gamma RIIIB-NA2/NA2 homozygotes for the development of SLE was 2.52 (95% confidence interval [CI]: 1.33-4.79). Among the patients with SLE, individuals with NA2/2 were significantly more likely to have lupus nephritis (P = 0.007). No association was observed between any of the Fc gamma R polymorphisms and RA. Significant linkage disequilibrium was detected between Fc gamma RIIIA and IIIB, but neither between IIA and IIIA, nor between IIA and IIIB. These observations may underscore the relevance of defective immune complex handling in the pathogenesis of SLE, or may suggest the presence of primarily associated gene(s) in linkage disequilibrium with Fc gamma R genes.
Hatta
Y
Y
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan 113-0033, Japan.
Tsuchiya
N
N
Ohashi
J
J
Matsushita
M
M
Fujiwara
K
K
Hagiwara
K
K
Juji
T
T
Tokunaga
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*
D017931:DNA Primers; D017452:Receptors, IgG