Análise genética de fenótipos cardiometabólicos complexosem população urbana e rural de Minas Gerais

Abstract

Cardiometabolic phenotypes such as cardiovascular diseases, obesity, insulin resistance, diabetes, high level of lipids were responsible for high mortality and its complications. Genetics could influence metabolism in many aspects and it could contribute to the high prevalence of these phenotypes. Therefore, the objective of this study was to research the cardiometabolic phenotypes with different strategies of genetic analyses using the estimate of heritability in a rural area, in Vale do Jequitinhonha and to associate the leptin receptor polymorphism (LEPR) Gln223Arg in an urban area, in Minas Gerais. Both studies were cross-sectional. The first study was conducted in the rural area of Virgem das Graças, Caju and São Pedro do Jequitinhonha, in which 931 individuals of 89 pedigrees were phenotyped. In the first study, the strategy of estimating heritability (h2), pleiotropy and its association with lipid levels, body mass index, waist circumference and blood pressure was evaluated. In the second study, the frequency of the LEPR Gln223Arg and the potentials associations with overweight, obesity, abdominal obesity and higher body fat was evaluated. The h2 estimates for the phenotypes evaluated ranged 28 to 60% and significant genetic correlations (g) were found for most pairs of phenotypes evaluated mainly among triglycerides - VLDL (g = 0.99), total cholesterol - LDL (g = 0.90), diastolic blood pressure - triglycerides (g = 0.63) and diastolic blood pressure - VLDL (g = 0.59), total cholesterol - triglycerides (g = 0.58). In general, genetic correlations were higher than the environmental correlations. Household effects have been found for HDL (c2 = 0.21, P < 0.001) and VLDL (c2 = 0.10, P = 0.010) and hypertension (c2 = 0.14, P = 0.015). Finally, to complete pleiotropy found between VLDL - triglycerides, it means that these phenotypes are controlled by a single gene or by a set of genes. Moreover, in the urban area, high levels of cardiometabolic phenotypes were observed: 19.4% of obesity, 26.8% of abdominal obesity, 49.1% of high body fat and 34.9% of high blood pressure. The prevalence of AA, AG and GG polymorphism LEPR Gln223Arg genotypes were 38.4%, 49.3 %, 12.3%, respectively. The LEPR Gln223Arg polymorphism was not associated with cardiometabolic phenotypes evaluated in the univariate analyses nor in the multivariate regression models. The significant heritabilities and pleiotropy were found in the rural area, which can direct potential genetic mechanisms of cardiometabolic phenotypes. However, LEPR Gln223Arg polymorphism was not associated with indicators of overweight in the urban area.