Objective. To determine whether inheritance of Fcγ receptor (FcγR) alleles conferring lower affinity for IgG binding increases the risk of developing lupus nephritis. Methods. We compared the frequency of lowaffinity alleles of two FcγR polymorphisms (FcγRIIA and FcγRIIIA) among 235 patients with systemic lupus erythematosus (SLE) and proven nephritis (nephritis patients) and among 352 SLE patients with no evidence of renal disease (non-nephritis control subjects). The ethnic distribution of patients in the study was 49% Caucasian, 20% Hispanic, 17% Asian/Pacific Islander, 12% African American, and 2% from other ethnic groups. All patients were genotyped for the FcγRIIA-131R/H and FcγRIIIA-158V/F polymorphisms. We used contingency table analysis to compare allele and geno. type distributions for nephritis patients and nonnephritis control subjects, including ethnic-specific strata. Multivariate logistic regression analyses included sex and disease duration as covariates. Results. Univariate and multivariate analyses demonstrated a striking association between the lowaffinity FcγRIIIA-158F allele and FF genotype and the risk of nephritis among Caucasians, but not among non-Caucasians (multivariate odds ratio [OR] 2.6 for Caucasians with FF genotype), (P = 0.0017). This association was even stronger among Caucasians with severe nephritis (OR 4.4, P < 0.0001). In contrast, inheritance of the low-affinity FcγRIIA-131R allele (and RR genotype) was not associated with an increased risk of lupus nephritis among any of the ethnic groups examined. Conclusion. The FcγRIIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians, but not among non-Caucasians. These results suggest that ethnic variation is critical in defining the specific genetic factors underlying the pathogenesis of SLE, and they have important prognostic and therapeutic implications as well.
|Original language||English (US)|
|Number of pages||8|
|Journal||Arthritis and Rheumatism|
|State||Published - 2001|
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