Association of the interleukin 15 (IL-15) gene polymorphisms with the risk of developing ulcerative colitis in Mexican individuals

Abstract

Interleukin 15 (IL-15) is a Th1-related cytokine that triggers inflammatory cell recruitment with implications for pathogenesis in ulcerative colitis. The IL-15 gene is located within a 35 kb region of the q28-31 locus of chromosome 4. In the present work, the role of IL-15 gene polymorphisms as susceptibility markers for UC was evaluated. Seven polymorphisms of IL-15 (rs3806798, rs10833, rs4956403, rs2254514, rs2857261, rs10519613, and rs1057972) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 199 Mexican patients with UC and 698 Mexican Mestizo healthy unrelated individuals. UC patients and healthy controls showed similar distribution of the rs3806798, rs10833, rs4956403, rs2857261, rs10519613, and rs1057972 polymorphisms. The rs2254514 polymorphism was significantly associated with decreased risk of UC as compared to controls under both dominant and additive models (OR 0.62, Pdom = 0.014 and OR 0.65, Padd = 0.02). The rs2254514 CC genotype was associated with young age at diagnosis <40 years (P = 0.03; OR 3.67). Five polymorphisms (rs1051613, rs2254514, rs2857261, rs1057972, and rs10833) were in strong linkage disequilibrium and were included in six haplotypes: H1 (ACAAC), H2 (CCGTC), H3 (CTAAT), H4 (CCAAT), H5 (CTAAC), and H6 (CCAAC). UC patients showed an increased frequency of the H6 haplotype (P = 0.005; OR 3.2) and a decreased frequency of the H5 haplotype (P = 0.031; OR 0.40). These results suggest that the IL-15 rs2254514 polymorphism might have an important role in the development of UC in the Mexican population. We were able to distinguish one risk and one protective uncommon haplotype for the development of UC.