Synergistic effect betweenIL-10 andbcl-2 genotypes in determining susceptibility to systemic lupus erythematosus

作者：Ruty Mehrian‐Shai, Francisco P. Quismorio, Gideon Strassmann, Mary M. Stimmler, David A. Horwitz, Rodanthi C. Kitridou, W. James Gauderman, John L. Morrison, Chaim Brautbar, Chaim O. Jacob · 发表于：Arthritis & Rheumatism · 年份：1998 · DOI：10.1002/1529-0131(199804)41:4<596::aid-art6>3.0.co;2-2 · 被引用次数：158 · 研究领域：Systemic Lupus Erythematosus Research、Diabetes and associated disorders、T-cell and B-cell Immunology

OBJECTIVE: To determine whether genes participating in programmed cell death, including bcl-2, IL-10, Fas-L, and CTLA-4, may contribute to the genetic predisposition to systemic lupus erythematosus (SLE). METHODS: First, intragenic markers for the bcl-2, IL-10, Fas-L, and CTLA-4 genes were characterized and their extent of polymorphism in normal populations was determined. The allelic distribution of these gene markers in a large Mexican American SLE cohort of 158 patients and 223 ethnically matched controls was determined using fluorescent-labeled primers and semiautomated genotyping. RESULTS: The bcl-2, Fas-L, and IL-10 loci showed significantly different allelic distribution in SLE patients compared with controls, indicating an association between these genes and SLE. No association was found between SLE and the CTLA-4 gene. Further analysis revealed a synergistic effect between susceptibility alleles of the bcl-2 and IL-10 genes in determining disease susceptibility. Alone, the presence of each of these alleles was associated with a moderate increase in SLE risk, while the occurrence of these alleles together increased the odds of developing SLE by more than 40-fold. CONCLUSION: The results suggest that individuals carrying specific genotypes of both bcl-2 and IL-10 are at significant risk of developing SLE.