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

Type 1 Diabetes mellitus (T1D) is caused by the immune-mediated destruction of insulin-producing islet beta 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).