Association of TNF promoter polymorphisms with type 1 diabetes in the South Croatian population

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic β cells. Tumor necrosis factor (TNF) is a pleotropic cytokine with potent immunomodulatory and inflammatory activity. Association studies of TNF polymorphisms and type 1 diabetes (T1DM) frequently demonstrated TNF involvement with T1DM. Although TNF may play an important role in the pathogenesis of T1DM, the genetic association of TNF region with the disease has not been conclusive because of the strong linkage disequilibrium with HLA genes. In this study, we examined two TNF promoter variants (rs1800629 at position -308, and rs361525 at position -238) for T1DM association in 233 patients and 144 controls from the population of South Croatia. A higher frequency of TNF -308 A allele and also, a more frequent specific - 308A -238G haplotype in T1DM patients were observed with a limited significance. However, we did not find strong evidence of association of TNF promoter polymorphisms with T1DM. In order to elucidate the true contribution of TNF to T1DM susceptibility in our population, more comprehensive studies with HLA adjustment in a larger sample are required.