Análise de biomarcadores de predisposição genética e ancestralidade para o Diabetes mellitus tipo 1 no estado do Maranhão

• Autor(a) principal: Azulay, Rossana Santiago de Sousa
• Data de Publicação: 2021
• Outros Autores: [e-mail]
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/16960
• topic: Type 1 diabetes; Y chromosome; Diabetes tipo 1; HLA; Cromossomo Y; Ancestralidade autossômica; Diabetes Mellitus Tipo 1 - Genética; Predisposição genética para doença; Cadeias HLA-DRB1 - Genética; Autosomal ancestry; CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::ENDOCRINOLOGIA

This study aimed to investigate the relationship between genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in patients with Type 1 Diabetes from an admixed Brazilian population. This cross-sectional study was carried out in a tertiary care center in the state of Maranhão, Brazil. We consecutively recruited patients with T1D, treated from October 2016 to July 2018. The individuals in the control group were blood donors. Patients and controls answered a questionnaire about their family members' declared ancestry and a clinical-demographic survey. For inference of autosomal ancestry, a panel of 46 autosomal informative insertion/deletion ancestry markers (AIM–Indels) was used and the HLA-DRB1, -DQA1 and -DQB1 typings were determined. The Y chromosome analysis was performed using 26 STR markers. The European autosomal ancestry was the largest contributor in our population (about 50% in both groups), followed by a similar percentage between African and Native American ancestry (about 25% each). We observed a predominance of the European Y chromosome, with the R1b haplogroup being the most frequent. In the analysis of the HLA system, the DRB1 * 03 and DRB1 * 04 alleles presented a risk odds ratio for association with T1D. The highest frequencies were of the DRB1 * 04 (30.26%) and DRB1 * 03 (29.93%) alleles; the DR3 / DR4 heterozygosity genotype (26.32%); the DR3-DQ2 haplotype (8,22%) and the HLA DRB1 * 03: 01-DQA1 * 05: 01-DQB1 * 02: 01 (DR3-DQ2) homozygote genotype (7.24%). We also found that when the Y chromosome was European, DRB1*03 and DRB1*04 homozygote and DRB1*03/DRB1*04 heterozygote genotypes were the most frequent. The findings suggested individuals from Maranhão have European origin as their largest component. The European patrilineal origin as evidenced by the higher frequency of the R1b haplogroup. The predominance of the HLA-DRB1* 03 and DRB1* 04 alleles conferring greater risk in our population and being more frequently related to the ancestry of the European Y chromosome, suggests that in our population the risk of T1D can be transmitted by European ancestors of our process miscegenation. However, the Y sample sizes of Africans and Native Americans were small and further research should be conducted with large mixed sample sizes to clarify this possible association.