Polymorphisms rs1800795 of interleukin-6 and rs2228145 of interleukin-6 receptor genes in euro-Brazilians with adult-onset type 1 diabetes mellitus

Abstract

Type 1 Diabetes mellitus (T1D) is caused by the immune-mediated destruction of insulin-producing islet β cells, and its pathogenesis involves cytokines. Genetic background may influence cytokine signals, and polymorphisms may determine their impact on T1D autoimmunity. Several polymorphisms in and close to Interleukin-6 (IL-6) and Interleukin-6 Receptor (IL-6R) have been identified as associated with pathological processes. We investigated the IL-6 promoter-174G>C (rs1800795) and IL-6R Asp358Ala (rs2228145) polymorphisms in 141 Euro-Brazilian patients with adult-onset type 1 diabetes (diagnosis > 18 years old) and 150 healthy controls, matched by gender and age. Genotyping for both polymorphisms was performed by PCR-RFLP. PCR fragments for rs1800795 with Hsp92II and rs1800795 with HindIII were resolved by 15% polyacrylamide gel electrophoresis. The polymorphisms in both groups were in Hardy-Weinberg equilibrium. IL-6 rs1800795 was not different between healthy controls and T1D subjects, showing 27.3% (95% CI, 20-35%) and 30.1% (23-38%) for the C minor allele (-174C), respectively. For IL-6R rs2228145, the genotype (P = 0.046) and allele (P = 0.021) were different in the groups. The frequencies for rs2228145 C minor allele (358Ala) were 34.7% (27-43%) and 44.0% (36-51%) for controls and T1D subjects, respectively. In conclusion, IL-6 rs1800795 was not associated with adult-onset T1D; however, IL-6R rs2228145 was associated with T1D development in adulthood, and carriers of the minor C allele are at increased risk for adult-onset T1D (OR = 1.48; 95% CI = 1.06-2.07).