RESUMO
The rs763361 single nucleotide polymorphism (SNP) within the CD226 gene has recently been reported as a novel susceptible locus for type 1 diabetes. The CD226 gene is implicated in the regulation of a number of cells involved in immune mechanisms leading to beta-cell destruction in type 1 diabetes. The aim of the present study was to confirm the association of the CD226 gene with type 1 diabetes in Estonian population. The TT genotype [odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.25-4.18, P = 0.0071) and the T allele (OR = 1.48, 95% CI = 1.11-1.98, P = 0.0084) of the rs763361 SNP were associated with the risk of type 1 diabetes. The current study replicates the novel association of the rs763361 SNP in susceptibility of type 1 diabetes and supports the CD226 gene as a susceptible candidate locus for type 1 diabetes outside the major histocompatibility complex region.
Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Diabetes Mellitus Tipo 1/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is considered an important regulator of T-cell activation. Polymorphisms within the PTPN22 gene have been suggested to confer susceptibility to autoimmune endocrine disorders. To evaluate the impact of a functional variation in the PTPN22 gene in type 1 (T1D) and type 2 diabetes (T2D), the PTPN22 C1858T single nucleotide polymorphism (SNP) was studied in the population of Estonian origin, including 170 T1D patients, 244 T2D patients and 230 controls. Using two methods for PTPN22 C1858T detection in parallel, we found that not only T1D but also T2D is associated with the PTPN22 1858T allele. The role of PTPN22 gene in the pathogenesis of T2D is yet unclear and needs further investigation.
Assuntos
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Estônia/epidemiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: In type 1 diabetes (T1D), the influence of age at diagnosis and of the IDDM1 and IDDM2 genetic susceptibility loci on the profile of beta-cell autoantibodies has been demonstrated. We studied these associations in a group of 92 patients (children, adolescents and adults, aged 2-62 years) with newly diagnosed T1D. METHODS: The prevalence of the HLA-DQB1*02 and *0302 alleles and of the classes of variable number of tandem repeats (VNTR) of the insulin gene (INS), and of beta-cell autoantibodies (GADA, IA-2A, ICA and IAA) was determined. Statistical analysis was performed using linear and logistic regression models. RESULTS: The presence of IAA, IA-2A and ICA, but not of GADA, was negatively associated with age at diagnosis. Younger patients were more likely to have multiple autoantibodies. There was a tendency of a higher prevalence of IAA in patients with the HLA-DQB1*02/0302 genotype or with the DQB1*0302 allele compared to patients lacking these markers. As a novel observation, the INS VNTR I/III genotype was significantly associated with the presence of GADA (OR = 4.79; p = 0.018). CONCLUSION: The association between the INS VNTR I/III genotype and GADA may suggest that in patients with T1D lacking the INS VNTR I/I genotype, the effect of other susceptibility factors prevails, which promotes the development of autoimmunity to beta-cell antigens other than insulin.