Interleukin 18 gene promoter polymorphisms in Latvian patients with rheumatoid arthritis

Abstract

Interleukin 18 (IL-18) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). There are controversial reports suggesting that IL-18 promoter polymorphisms may be an independent marker of RA susceptibility. The aim of the present study was to determine whether polymorphisms of the IL-18 gene promoter in positions -607 (rs 1946519) and -656 (rs 1946518) are associated with RA, and its characteristics in the Latvian population. We examined 105 patients with RA diagnosed according to the criteria of the American College of Rheumatology. DNA and phenotypic data from a healthy control population was obtained from Genome Database of Latvian Population. Genotypes were obtained by direct sequencing. Single-nucleotide polymorphisms (SNPs) were studied and frequencies of alleles and genotypes were compared between patients and controls. A P value less than 0.05 was accepted as statistically significant. There were no significant differences in the distribution of alleles and genotypes between RA patients and the control group. The frequencies of IL-18-607C/A and -656G/T genotypes differed between patients and the control group in women (P = 0.084 and 0.097). Heterozygous genotypes -607CA and -656GT occurred more frequently in the RA group than in the control (P = 0.046, P = 0.060), and this difference was also significant for the only women groups (P = 0.041,P = 0.054). The heterozygous states -607CA and -656GT of IL-18 gene affect susceptibility to RA. On the basis of investigated IL-18 polymorphisms, female patients with RA seem to represent a separate disease subgroup.