Association of Fcγ receptor IIb and IIIb polymorphisms with susceptibility to systemic lupus erythematosus in Thais

Abstract

We recently reported association of a newly identified polymorphism of Fcgamma receptor (FcgammaR) IIb, I232T, with systemic lupus erythematosus (SLE) in Japanese. To date, information on FcgammaR genotypes and their association with SLE is limited in South-east Asian populations. To gain further insight into the role of FcgammaR polymorphisms in the genetic predisposition of SLE, association of FcgammaRIIa-H131R, IIb-I232T, IIIa-F176V and IIIb-NA1/NA2 (HNA-1a/1b) polymorphisms with SLE was analyzed in the Thai population, using case-control association analysis. FcgammaRIIb-232T/T and IIIb-NA2/NA2 genotypes were associated with SLE with the odds ratio of 2.55. Genotype relative risk analysis revealed significant association of IIb-232T/T and IIIb-NA2/NA2, and a tendency of association of the IIIa-176F/F genotype. Moreover, carriers of FcgammaRIIa-131R were significantly increased in patients with lupus nephritis. Significant linkage disequilibrium was present among FcgammaRIIb, IIIa and IIIb, and two-locus analyses suggested that the tendency of association of FcgammaRIIIa could derive from linkage disequilibrium with IIb and IIIb. These results provided evidence that FcgammaR polymorphisms may be an important predisposing factor also in Thais in a complex manner.

Association of a transmembrane polymorphism of Fcγ receptor IIb (FCGR2B) with systemic lupus erythematosus in Taiwanese patients

“…Our data support previous findings in 3 other Asian populations (29,32,33). However, the Fc␥RIIb Ile/ Thr187 polymorphism may require epistatic interaction with other genes to express the autoimmune phenotype.…”

“…There were significant differences in the genotype distribution between patients with and without pleural effusion ( 2 ϭ 6.59, P ϭ 0.037 by 3 ϫ 2 contingency Strong association of the FCGR2B Ile187Thr polymorphism and SLE in Asian populations. Several published association studies suggest that the FCGR2B minor allele, Thr187, is a risk factor for disease in Thai, Japanese, and Chinese populations, but not in American or Swedish Caucasian or in African American populations (28,29,(32)(33)(34). This differential result does not seem to reflect different population allele frequencies, since the frequencies of the Thr187 allele in these Asian 142 (51) 105 (38) 29 (11) 142 (51) 134 (49) 389 (70) 147 (56) 87 (33) 29 (11) 147 (56) 116 (44) 381 (72) 145 (28) Oral ulcer Positive (n ϭ 112) 59 (53) 42 (38) 11 (10) 0.752 59 (53) 53 (47) 0.853 160 (71) 64 (29) 1.000 Negative (n ϭ 239)…”

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

“…Hence, we observed no effects of OPN deletion on CIA, as suggested by Blom et al (8) and in contrast to the findings reported by Yumoto et al (7), using another arthritis model, the CAIA model. There are several conceivable reasons for this contradiction.…”

“…Moreover, we have demonstrated that expression of OPN is enhanced in arthritic joints of both RA patients (5) and mice with collagen-induced arthritis (CIA) (6). In addition, it has been reported that OPN Ϫ/Ϫ mice are resistant to experimental autoimmune encephalomyelitis (EAE) (3) and to anti-type II collagen (CII) antibody-induced arthritis (CAIA) (7). However, a conflicting report suggests that EAE, CIA, and CAIA are fully inducible without OPN (8), and therefore, the role of OPN in the above inflammatory diseases remains controversial.…”

“…Genotyping methods were as described in detail previously (3,7,8,15). Association between FCGR polymorphisms and SLE was examined by the transmission disequilibrium test (TDT) (16) using GeneHunter version 2.1 software (17) and by the pedigree disequilibrium test (PDT) using PDT software version 3.12 (18), as well as by the family-based association test (FBAT) (19).…”