Association of interleukin-1 gene cluster polymorphisms and haplotypes with multiple sclerosis in an Iranian population.

Abstract Multiple sclerosis (MS) is a multi-factorial autoimmune disease of the central nervous system. The exact etiology of MS is still unknown. Due to the important roles that cytokines play as mediators in immune and inflammatory responses, we have evaluated the association of IL-1 gene cluster polymorphisms and haplotypes with MS susceptibility in 306 unrelated MS patients and 312 healthy matched controls. A significant association was found for the IL-1β + 3953 T allele [OR = 1.43, 95% CI (1.14–1.79), P value = 0.002, Pc  = 0.01] and for IL-1β + 3953 T/T genotype and MS risk [OR = 1.92, 95% CI (1.25–2.96), P value = 0.005, Pc  = 0.01]. Interestingly, the genotypes of the polymorphisms remained significant under recessive, co-recessive and dominant models. However, no significant differences were found between MS patients and controls in the genotype and allele frequencies of the IL-1β − 511, − 31 and IL-1Ra polymorphisms. Haplotype analysis for IL-1β − 31 and IL-1β − 511, with moderate linkage disequilibrium (LD), using the EM algorithm revealed a significant global association of haplotype differences between the two groups. Lower presence of two haplotypes (H3: C-T and H4: T-C) was observed in the MS patients than healthy controls. However, after applying Bonferroni's correction the differences were not significant. To our knowledge, this is the first study reporting the association of the IL-1β + 3953 gene polymorphism and MS susceptibility.