Estudo de polimorfismos genéticos do sistema renina-angiotensina e do sistema β-adrenérgico e relações de ancestralidade em uma amostra de indivíduos hipertensos miscigenados da população do estado do Rio de Janeiro

• Ano de defesa: 2015
• Autor(a) principal: Machado, Yasmin Lemos Rollemberg Cruz
• Orientador(a): Silva, Dayse Aparecida da
• Banca de defesa: Brandão, Andréa Araujo , Seixas, Teresa de Souza Fernandez
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Biologia Humana e Experimental
• Departamento: Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes
• País: BR
• Palavras-chave em Português: Hipertensão arterial sistêmica. Indivíduos miscigenados. Polimorfismos genéticos. Sistema renina-angiotensina. Beta-adrenérgico. Ancestralidade genômica. AIMs-Indels.; Hipertensão; Polimorfismo (Genética); Sistema renina-angiotensina; Receptores Adrenérgicos beta
• Palavras-chave em Inglês: Essential hypertension; Admixed subjects.Genetic polymorphisms; Renin-angiotensin system; Beta-adrenergic; Ancestry genomic; AIMs-Indels
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::GENETICA::GENETICA HUMANA E MEDICA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/7887

Hypertension is a highly prevalent physiological multifactorial disorder, triggered by the integration of environmental and genetic factors. Association studies have used molecular markers (genetic polymorphisms) to investigate a possible predisposition.However, in admixed populations, such as Brazil, erroneous associations between a particular disease and an allele (spurious associations) may occur when naturally predisposed ethnic groups are over-represented in the sample (population stratification). From that, we investigated the variation of the circulatory metabolism gene polymorphisms and the association of this variant with the genetic ancestry in a sample of healthy and hypertensive admixed individuals from population of the state of Rio de Janeiro. DNA samples obtained from 178 normotensive and 113 hypertensive individuals were genotyped for four polymorphisms hypertension-associated (I/D angiotensin-converting enzyme I, Ser49Gly and Arg389Gly of beta1-adrenergic receptor and M235T of angiotensinogen) and 46 ancestry informative markers (AIMs-Indels); their genotypic, allelic frequencies and ancestry estimates were calculated and compared between the clinical groups.Hypertensive individuals had a mean age greater than normotensive ones (p <0.000; α=0.05), with individuals of both gender equally distributed between them. In all clinical sample groups, European alleles (48-60%) were over-represented, followed by the African (25-39%) and, finally, Amerindians (12-14%), exhibiting a predominant European genetic in individuals from our population.The presence of hypertension occurred in 63.2% of individuals of African descent, 43.0% of mixed race and only 27.0% of euro-descendants (2 = 11,889, p=0.003). A higher prevalence of the II genotype was observed in hypertensives compared to normotensives (21.2% vs. 10.7%; 2 = 0.023 p = 7.549) and the MM genotype in normotensive compared to hypertension (21.9% vs. 8.8% 2 = 10.737 p = 0.005). There was no significant difference in the distribution of genotypes of Arg389Gly and Ser49Gly polymorphisms between normotensives and hypertensives. According to the individual genetic ancestry, there was no significant difference in the pattern of distribution of genotypes of either genetic polymorphisms. Normotensive and hypertensive subjects had similar genetic diversity for both genetic polymorphisms (44.34% and 46.11%) and for AIMs (38.85% and 40.37%), reflecting a high degree of admixture. Thus, it may be suggested that African ancestry exerted influence on the prevalence of hypertension in the sample and that despite the ACE and M235T polymorphisms have presented different distributions between normotensive and hypertensive individuals, genetic ancestry had no effect on how all the genetic polymorphisms evaluated are distributed.