Distribución de polimorfismos del gen del antígeno-4 del linfocito T citotóxico en población chilena con diabetes mellitus tipo 1 / Distribution of cytotoxic T lymphocyte antigen-4 gene polymorphisms in Chilean population with type 1 diabetes mellitus

Background: Cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule is an important regulator of T cell activation involved in the down-regulation of immune response. Their polymorphisms +49 A/G and CT60 have been suggested to confer susceptibility to autoimmune endocrine disorders. The aim of this study was to determine the association of CTLA-4 gene polymorphisms with T1D in the Chilean population. We also wanted to study if the combined haplotypes of +49 A/G and CT60 had an impact on risk for T1D. Methods: To evaluate the impact of allelic variants CT60 and +49 A/G SNPs were studied in a Chilean population, including 248 T1D patients and 160 controls. Genotypes of both polymorphisms of CTLA-4 gene were determinate by PCR-restriction fragment polymorphism (PCRRFLP).Results: No statistical differences were observed when comparing patients with diabetes and controls for both CTLA-4 genotypes. However, the haplotype analysis between CT60 and +49 A/G showed an interesting combination of risk conformed by G*G combination with an OR of 1.648 [1.19- 2.28], (p = 0.002). Conclusions: The G*G haplotype could be a risk marker in patients with T1D in Chilean population.

Frecuencia de polimorfismo C1858T del gen PTPN22 y marcadores de autoinmunidad en pacientes chilenos con diabetes tipo 1 y enfermedad celíaca / C1858T polymorphism of protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene in diabetic and celiac patients

Background: A genetic polymorphism called C1858T of protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene has been associated with autoimmune diseases Aim: To describe the association between two autoimmune diseases, namely type 1 diabetes (T1D) and celiac disease (CD)and tyrosine phosphatase gene polymorphisms (variant C1858T of PTPN22). Subjects and Methods: C1858T single-nucleotide polymorphism within the PTPN22 gene was genotyped in 209 patients with T1D, 43 celiac patients and 100 healthy controls. Results: CC gene frequency was 0.906 and 0.790 in CD patients and controls respectively ( p < 0.01). All analyzed groups had a low frequency of the TT genotype. Compared with the other study groups, patients with T1D had a low frequency of CC genotype (0.636). Also, in these patients, there was a non-significant association between CC genotype and islet cell IA-2 auto antibodies (p < 0.065). Among CD patients, CC genotype was significantly associated with anti-transglutaminase or anti endomysial antibodies (p < 0.03). Conclusions: These results confirm the association of the genetic variant C1858T of PTPN22 with CD. In contrast to published data, this association was not found in T1D patients.