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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Epidemiology and Disease Control Subcommittee 3 (EDC)
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University of Cincinnati
Schools of Medicine
United States
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Morrison, John A; Barton, Bruce A; Biro, Frank M et al. (2003) Sex hormones and the changes in adolescent male lipids: longitudinal studies in a biracial cohort. J Pediatr 142:637-42
Morrison, John A; Sprecher, Dennis L; Biro, Frank M et al. (2002) Serum testosterone associates with lower high-density lipoprotein cholesterol in black and white males, 10 to 15 years of age, through lowered apolipoprotein AI and AII concentrations. Metabolism 51:432-7
Rice, T; Rankinen, T; Province, M A et al. (2000) Genome-wide linkage analysis of systolic and diastolic blood pressure: the Quebec Family Study. Circulation 102:1956-63
Morrison, J A; Sprecher, D L; Biro, F M et al. (2000) Estradiol and testosterone effects on lipids in black and white boys aged 10 to 15 years. Metabolism 49:1124-9
Morrison, J A; Barton, B A; Biro, F M et al. (1999) Overweight, fat patterning, and cardiovascular disease risk factors in black and white boys. J Pediatr 135:451-7
Morrison, J A; Jacobsen, D W; Sprecher, D L et al. (1999) Serum glutathione in adolescent males predicts parental coronary heart disease. Circulation 100:2244-7
Rice, T; Perusse, L; Bouchard, C et al. (1999) Familial aggregation of body mass index and subcutaneous fat measures in the longitudinal Quebec family study. Genet Epidemiol 16:316-34
Borecki, I B; Blangero, J; Rice, T et al. (1998) Evidence for at least two major loci influencing human fatness. Am J Hum Genet 63:831-8
Morrison, J A; Sprecher, D L; Biro, F M et al. (1998) Sex hormones and lipoproteins in adolescent male offspring of parents with premature coronary heart disease and a control group. J Pediatr 133:526-32
Morrison, J A; Barton, B A; Biro, F M et al. (1998) The conjoint trait of low high-density lipoprotein cholesterol and high triglycerides in adolescent black and white males. Metabolism 47:514-21

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