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.

Association between Recipient IL-15 Genetic Variant and the Prognosis of HBV-Related Hepatocellular Carcinoma after Liver Transplantation

“…Although some researches have reported the association of IL-15 with the clinical outcome of HCC, studies of the genetic variants in the IL-15 gene on HCC recurrence and prognosis after LT are few. In this study, the overall frequency of IL-15 rs10519613 CC, CA, and AA genotypes were 33.5%, 47.8%, 18.7%, respectively; our data were similar to that of the previous study in other population [ 26 ]. Our results revealed that recipient IL-15 rs10519613 polymorphisms (CA/AA versus CC genotype; A versus C allele) were significantly associated with HCC recurrence after LT.…”

Mucosal interleukin‐8 expression as a predictor of subsequent relapse in ulcerative colitis patients with Mayo endoscopic subscore 0

“…Many reports have discussed the relationship between mucosal cytokine expression in the colonic mucosa of patients with active UC and its pathogenesis, 21 and few reports have analyzed cytokine expression in the mucosa endoscopically, such as MES 0, during deep remission. The 22 cytokines that we analyzed in this study, including TNF‐α, 22 IFN‐γ, 23 IL‐1β 24 , IL‐2, 24 IL‐4, 25 IL‐5, 26 IL‐6, 27 IL‐7, 28 IL‐8, 29,30 IL‐9, 31 IL‐10, 32 IL‐12, 11,33 IL‐13, 34 IL‐15, 35 IL‐17A, 36 IL‐17F 38 , IL‐18, 37 IL‐21, 38 IL‐22, 39 IL‐23, 40 IL‐27, 41 and IL‐33, 42 have been previously reported to be associated with the pathogenesis of UC. Among these cytokines, the expression of 10 cytokines including IL‐2, IL‐4, IL‐8, IL‐10, IL‐12, IL‐15, IL‐17A, IL‐21, IL‐23, and IL‐33 significantly increased in the rectal mucosa of patients with UC who showed subsequent relapse compared with remission in the present study.…”

IL-15 negatively regulates curdlan-induced IL-23 production by human monocyte-derived dendritic cells and subsequent Th17 response

“…In both celiac and IBD patients, IL-15 levels and the cellular sources of IL-15 have been shown to be increased in the intestine [29–31]. In fact, some SNP variants of Il15 have been identified as risk factors for IBD [32]. In the murine models, IL-15 was shown to negatively regulate Th17 cells.…”