Influência da ancestralidade genética na distribuição de alelos e haplótipos HLA -DR e -DQ em uma amostra de pacientes com Diabetes Mellitus Tipo 1

• Autor(a) principal: Gabrielli, Aline Brazão
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/7873
• topic: Diabetes type 1; Genetic ancestry; HLA; Human Leukocyte Antigen; Mixed population; Ancestry; AIM-Indels; Diabetes Mellitus tipo 1; Hereditariedade humana; Antígenos de histocompatibilidade HLA; Antígenos HLA-DR; Antígenos HLA-DP; Diabetes Mellitus tipo 1; Ancestralidade genética; HLA; AntígenoLeucocitário Humano; População miscigenada; AIM-Indels; CNPQ::CIENCIAS BIOLOGICAS::GENETICA

It is undeniable the influence of human leukocyte antigen class II DR-DQ in the outbreak of type 1 diabetes mellitus. However, the frequency of alleles and haplotypes associated with the disease and their respective effect is diversified among different ethnic groups and geographic regions. Studies in admixed or not Caucasian populations are scarce and face inadequate population stratification, generating spurious associations. In view of this, this study aimed to investigate the genetic ancestry from the distribution of HLA-DRB1, -DQA1 -DQB1 and within ethnic groups observed in the Brazilian population. The genetic ancestry of 972 DM1 patients from different regions of the country was estimated using 46 informative markers of ancestry (AIMs), of whom 479 had the HLA class II loci typed. With the inference of ancestry was observed that the study sample was not properly stratified using the ethnic self-declaration only. Across the country there was a predominance of European ancestry with some regional differences. It was not possible to see differences in the frequencies of HLA haplotypes between ethnic groups, but we found significant differences in the diversity of alleles between groups, the presence of heterozygotes DR3 / DR4 and influence of ethnic origin of haplotype and related effects even at the age diagnosis. In the DM1 Brazilian population the presence of protective haplotypes was higher than expected (28%), of these, 41% was found in the Caucasian group. The presence of protective haplotypes can justify the average age at diagnosis higher observed in our population when compared to the findings of the American population. These data help us understand the genetic variation present in the brazilian population and also the differences in the clinical presentation of type 1 diabetes in different ethnic groups.