Detection and functional evaluation of -262A/T and -188A/G polymorphisms of SLAM gene in patients with systemic lupus erythematosus

Abstract

Objective. Signaling lymphocytic activation molecule (SLAM) has been related to the pathology of systemic lupus erythematosus (SLE) through regulation of T cell-dependent humoral immune responses. We investigated the functional associations of the -262A/T and -188A/G polymorphisms of SLAM in Chinese patients with SLE. Methods. Genotyping of -262A/T (rs2295614) and -188A/G (rs2295613) in SLAM was carried out in 248 cases and 278 controls. Promoter activities of haplotypes on the SLAM gene were evaluated with the dual-luciferase reporter system. The mRNA expressions of SLAM on peripheral blood mononuclear cells (PBMC) of SLE patients with different genotypes were determined by real-time polymerase chain reaction. Results. Frequencies of -262Aallele and -188G allele were significantly higher in SLE patients than in controls. Haplotype analysis and multifactorial logistic regression analysis showed that individuals with the AG/AG haplotype had increased susceptibility to SLE (p = 0.002, OR 1.478, 95% CI 1.152-1.897). In response to PHA stimulation, the SLAM mRNA expression on PBMC of SLE patients was significantly higher in -262A-188G haplotype homozygotes compared with -262A-188G heterozygotes and individuals with other genotypes. Conclusion. Our findings suggest that -262A-188G haplotype in the SLAM gene promoter contributes to the risk of SLE by increasing the expression of SLAM. The Journal of Rheumatology Copyright © 2010. All rights reserved.