Type 1 diabetes susceptibility determined by HLA alleles and CTLA-4 and insulin genes polymorphisms in Brazilians Suscetibilidade ao diabetes tipo 1 determinada por alelos de HLA e polimorfismos nos genes CTLA-4 e insulina em brasileiros

Introduction: Type 1A diabetes mellitus (T1ADM) is a multifactorial disease in which genetic and environmental aspects are important to its development. The association of genetic va- riations with disease has been demonstrated in several studies; however, the role of some gene loci has not yet been fully elucidated. Objective: To compare the frequency of HLA alleles and polymorphism in CTLA-4 and insulin genes in Brazilians with T1ADM and individuals wi- thout the disease, as well as to identify genetic markers that are able to discriminate between diabetic and non-diabetic individuals. Methods: The presence of HLA DQB1, DQA1 and DRB1 alleles, as well as the -2221 MspI polymorphism in the insulin gene and 49 A/G in the CTLA-4 gene were identified by the "Time-resolved fluorometer" technique after hybridization with probes labeled with Eu (III) / Sm (III) and Tb (III). Results: The DQB1 *0302 and DQA1 *03 alleles were identified as predisposed to T1ADM, and the DQB1 *0301 allele presented a pro- tective effect against the disease. The DQA1 label proved to be able to differentiate between 71.13% of the diabetic and non-diabetic individuals. This value increased to 82.47% when the DQB1 label was added. No significant difference in the frequency of polymorphisms in the insulin and CTLA-4 genes was observed between the two groups. Conclusions: The genetic markers that best characterized and discriminated diabetic and non-diabetic individuals were the HLA DQA1 and DQB1.alleles. Arq Bras Endocrinol Metab. 2009;53(3):368-73.