Independent association of HLA-DR and FCgamma receptor polymorphisms in Korean patients with systemic lupus erythematosus.

Abstract

To determine the distribution of HLA-DR type and FcgammaRIIa/IIIa polymorphisms, and to analyse the combined effects of these genes for susceptibility in Korean systemic lupus erythematosus (SLE) patients. A total of 299 SLE patients meeting 1982 ACR criteria and 144 Korean disease-free controls were enrolled. Genotyping for the FcgammaRIIa 131 R/H and FcgammaRIIIa 176 F/V was performed by polymerase chain reaction (PCR) of genomic DNA using allele-specific primers. HLA-DRB1 typing was performed by the PCR-SSOP method. There was significant skewing in the distribution of the three FcgammaRIIa genotypes between the SLE patients and the controls [P = 0.002 for R/R131 vs R/H131 and H/H131, relative risk (RR) 2.6 (95% CI 1.3-5.2)], but not in FcgammaRIIIa genotypes. HLA-DRB1*15 allele was significantly more prevalent among SLE patients than the control population [P < 0.02, RR = 1.7 (1.1-2.6)]. HLA-DRB1 genotypes or allele frequencies of the SLE patients with nephritis did not differ significantly from those of the SLE patients without nephritis. We analysed the combined effects of the two candidate genes on SLE susceptibility. HLA-DRB1*15 allele was a significant predictor of SLE in individuals who were not homozygous for FcgammaRIIa-R/R131 [RR = 2.1 (1.2-3.7), P < 0.008], and the FcgammaRIIa-R/R131 genotype vice versa [RR = 5.3 (1.9-15.4), P < 0.001]. However, an additive or synergistic effect of both susceptible genes on relative risk for SLE was not evident. Our results suggest that FcgammaRIIa-R/R131 homozygote and HLA-DRB1*15 allele are independent risk factors in Korean SLE patients without additive or synergistic effects.