GENETIC EPIDEMIOLOGY OF SEX HORMONES AND LIPOPROTEINS

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An extension and expansion of the study Sex Hormones and Lipoproteins in Adolescent Males (RO1-HD-18281) to include all first degree relative and the oldest paternal uncle or aunt of a random subset of the white male student and the offspring of early CHD patient populations is proposed to assess: 1) the contribution of sex steroid hormones to the risk profiles of adult men beyond the traditional CHD risk factors; 2) the risk of developing CHD at an individual level in the adolescent population using fitted logistic models; 3) the nature of family resemblance for such risk estimates; and 4) the relative contributions of genetics and shared household environments to the familial associations, singly and jointly, of sex steroid hormones, lipids, lipoprotein cholesterols, apolipoproteins, blood pressure and ponderosity. Thus, this study will provide unique insights into the genetic basis of the joint associations of sex steroid hormones and traditional CHD risk factors. Specifically, we will quantitate total and free testosterone (T), estradiol (E2), testosterone- estrogen binding globulin (TEBG), dehydroepiandrosterone sulfate (DHEAS), total, HDL and LDL cholesterol, triglycerides, HDL2 and HDL3 subfractions, apolipoproteins A1, A2, B (and determine E isoforms), height, weight, skinfolds and diet on 200 white male students, 100 offspring approximately 1050 first degree relatives, and 300 paternal uncles or aunts. We will obtain these measures on two occasions one year apart. Preliminary data from our current study (HD 18281) indicate that the offspring have 1) sex steroid hormone profiles which differ from those of the (healthy) school-based subjects; 2) greater mean levels of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B than the school-based subjects; and 3) that reductions in adolescent male HDL2 precede the decrease in total HDL-C. We will conduct these studies in the families of the same white school students and offspring with whom we have been working successfully (greater than or equal to 93% retention rate at the end of Visit 5) for the past 21/2 years. The proposed research is expected to improve significantly our knowledge of CHD risk, of the familial associations and interactions of coronary risk factors including sex steroid hormones and lipids. Thus, this study should indicate possible areas for intervention.