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Genetic epidemiological investigation of blood pressure and its metabolic correlates in Mexican American children
Chittoor, Geethavani
Chittoor, Geethavani
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Abstract
Anthropological geneticists have applied methods and theories used in the analyses of normal variation to study complex diseases and their associated risk factors. This dissertation is an investigation of blood pressure (BP) and its correlation with metabolic syndrome (MS)-related traits using a cohort of Mexican American children. The major goals of this dissertation are to: (1) examine various MS-related traits in Mexican American children such as obesity, dyslipidemia, hypertension, impaired fasting glucose, impaired glucose tolerance, insulin resistance, and microalbuminuria; (2) determine the genetic influences on measures of systolic blood pressure (SBP), diastolic blood pressure (DBP) and other variables (e.g., fasting insulin, fasting glucose, microalbuminuria, lipids, and adiposity measures) by estimating heritabilities; (3) examine common genetic influences (i.e., pleiotropy) on BP and its related MS-related traits (e.g., obesity) by using bivariate analyses; and, (4) investigate potential genetic-by-environment (e.g., obesity and lifestyle factors such as physical activity) interaction influences on BP. This study examined 604 nondiabetic Mexican American children and adolescents aged 6-17 years. Variance component analysis is used for both univariate and multivariate models to partition the total phenotypic variation of a given trait(s) into genetic and environmental components. The results indicate high to moderate occurrence of various MS risk factors in these children (overweight = 52%, obesity = 33%, low HDL = 24%, prediabetes = 15%, increased abdominal obesity = 14%, and high blood pressure = 13%). These findings signify the increasing burden of disease risk in these children due to elevated BP, higher prevalence of obesity, and lower insulin sensitivity. The heritabilities of SBP, DBP, and elevated BP are high in this population, suggesting that additive genetic factors strongly influence BP. The relative contributions of both genetic and environmental influence were quantified, genes accounted for 25 - 85% of the phenotypic variation in measures of blood pressure, adiposity, lipids, microalbuminuria, insulin and glucose, whereas age, gender, puberty and physical fitness and other environmental covariates accounted for <45% of the total phenotypic variance. Thus, the clustering of MS-related traits due to pleiotropy in adults is also demonstrable in children of Mexican American ethnic background.
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Date
2009-12-31
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University of Kansas
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Physical anthropology