SYNERGISTIC EFFECT BETWEEN IL-10 AND bcl-2 GENOTYPES IN DETERMINING SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS

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Abstract

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, andCTLA-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 thebcl-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 bothbcl-2 and IL-10 are at significant risk of developing SLE.

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