Genetic and environmental effects on obesity and insulin resistance : findings in youth

Overweight and obesity have adverse metabolic effects on blood pressure, blood lipids and insulin resistance, consequently increasing the risk of chronic diseases such as type 2 diabetes, cardiovascular diseases, and even certain forms of cancer. Together with abdominal obesity, insulin resistance plays a principal role in initiating and perpetuating the pathological manifestations of the metabolic syndrome. Obesity results from the combined effects of genes, environment and lifestyle. In this context, an understanding of these effects of lifestyle and genes on obesity and also their interactions is important to provide a basis for determining the role they could have on the development and prevention of obesity. The main aim of the current thesis was to investigate the association of several candidate genes (the beta-2 adrenergic receptor gene [ADRB2J, the nitric oxide synthase-3 gene [NOS3] and the apolipoprotein-B gene [APOBl) with adiposity, and to assess whether the previously identified common variants in the fat mass and obesity-associated (FTO) gene, near the insulin induced gene 2 (INSIG2) and the melanocortin 4 receptor (MC4R) gene identified in GWA studies were associated with adiposity and insulin resistance in European-American (EA) and African-American (M) youth in both cross-sectional and longitudinal studies. We used data from the Georgia Cardiovascular Twin (Georgia CV Twin), the Lifestyle, Adiposity and Cardiovascular Health in Youths (LACHY) and the Adiposity Prevention through Exercise (APEX) studies in the cross-sectional investigations, and the Georgia CV Twin and Blood Pressure Stress cohorts in the longitudinal studies. Furthermore, the potential interaction of these common variants with ethnicity, gender or lifestyle behaviors (diet and physical activity) was investigated. In addition, we estimated the influence of genetic and environmental factors on fasting and 2-h glucose and insulin in a multivariate fashion in a large sample of UK female twins. ...

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