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P070. Genetic polymorphisms of interleukin 15 (IL-15) in patients with ulcerative colitis

J. Yamamoto-Furusho1, J. De-Leon-Rendon1, G. Vargas-Alarcon2, 1IBD Clinic, Instituto Nacional de Ciencias Medicas y Nutricion, Gastroenterology, Mexico, Mexico, 2Instituto Nacional de Cardiologia, Molecular Biology, Mexico

Background

Interleukin 15 (IL-15) is a Th1-related cytokine that triggers inflammatory cell recruitment with implications for pathogenesis in ulcerative colitis. The interleukin 15 gene is located within a 35 kb region of q28–31 locus of chromosome 4. No previous studies have reported this novel association between UC and IL-15 polymorphisms. In the present work, the role of IL-15 gene polymorphisms as susceptibility markers for UC was evaluated.

Methods

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. Polymorphisms (rs3806798, rs10833, rs4956403, rs2254514, rs2857261, rs10519613, and rs1057972) were genotyped using 5' exonuclease TaqMan genotyping assays on an ABI Prism 7900 HT Fast Real-Time PCR System. Gene frequencies of IL-15 polymorphisms on patients and controls were obtained by direct counting. The Hardy-Weinberg equilibrium was evaluated by chi-square test. Statistical significance was considered as p < 0.05. Pair wise linkage disequilibrium (LD, D') estimations between polymorphisms and haplotype reconstruction were performed with Haploview version 3:32 (Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA).

Results

UC patients and healthy controls showed similar distribution of the rs3806798, rs10833, rs4956403, rs2857261, rs10519613, and rs1057972 polymorphisms. A moderate increased frequency of the rs2254514 CC genotype was observed in UC patients when compared to healthy controls (p = 0.04, OR = 1.62) and 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). In the subgroup analysis, the rs2254514 CC genotype was associated with young age at diagnosis <40 years (p = 0.03, pC=0.05, OR = 3.67 95% CI: 1.13–15.9).

Conclusion

These results suggest that IL-15 rs2254514 polymorphism might have an important role in the development of UC. In our study was possible to distinguish one risk and one protective uncommon haplotypes for developing UC.