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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 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 18 (3): gmr18260 L.P. Campos et al. 2 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).

Type 1 diabetes mellitus (T1D) is considered a polygenic disease that is influenced by environmental factors and autoimmune responses to autoantibodies, resulting in metabolic abnormalities. Tyrosine kinase 2 (TYK2) is involved in type I interferon signaling in beta cells, and TYK2 polymorphism rs2304256 has been associated with T1D. We investigated polymorphism rs2304256 (TYK2) in a case-control study of Euro-Brazilians with T1D manifested during childhood and adulthood. We studied 307 individuals manifesting clinical signs of type 1 diabetes (151 children below 14 years of age and 156 adults with diagnosis after 18 years of age). The control samples consisted of 169 healthy children and 150 healthy adult subjects. T1D groups had inadequate glycemic control because fasting glucose and mean HbA1C concentrations were significantly higher than in the control groups. Real-time PCR with

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Several studies have described an association between cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphism and type 1 diabetes mellitus (T1D) in some ethnic populations, and a lack of association in other populations. Differences in the contribution of the genetic background of T1D onset are age dependent. We conducted a case-control study of a T1D Brazilian population, in which a possible association of rs231775 (+49A/G) and rs5792909 (-318C/T) polymorphisms in CTLA-4 with T1D was evaluated. These polymorphisms were genotyped in 150 childhood-onset (age  14 years old) and 150 adult-onset (age >18 years) patients with diabetes and nondiabetic healthy individuals (150 children and 150 adults). PCRrestriction fragment length polymorphism (rs5792909) and TaqMan® fluorescent probe (rs231775) methodologies were used for genotyping. The polymorphisms were in Hardy-Weinberg equilibrium. There was no difference in genotype and allele frequency between the patients with T1D and non-diabetic controls. The frequencies for childhood-T1D and adulthood-T1D, for the rs231775 G-allele (95% CI) were 39.0% (31-47) and 37.3% (30-46), and for the T-allele of the rs5792909 polymorphism they were 5.0% (3-7%) and 2.7% (1-4%), respectively. We did not ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 20 (2): gmr18817 M.M. Sousa et al. 2 identify an association of CTLA-4 rs231775 and rs5742909 polymorphisms with adult-or childhood-onset T1D in a Euro-Brazilian population in Southern Brazil.