The goal of this project is to conduct a genetic epidemiologic study of coronary heart disease (CHD) risk factors in black and white girls who are participating in an ongoing NHLBI-sponsored longitudinal study of obesity development during pubescence. NHLBI Growth and Health Study, NGHS, is an epidemiologic study of 2,379 black and white girls, ages 9-10 years at entry, who have been followed annually for the past 4 years. Currently, Year 0 follow-up is being completed, and 2 more years of follow-up are planned. The cohort retention rate at the end of Year 04 was 91% of the original cohort. Our proposed study is an independent research project which is an ancillary study to the NGHS and which utilizes the extensive biological and environmental information available from the NGHS core data base. We propose to obtain blood samples from 1,750 girls seen at their followup examinations in Year 7, to determine genotypes at those loci known to be implicated in lipid metabolism and obesity. Both protein [apolipoproteins C-II, D, and E and LP(a)] and DNA [apolipoprotein B, lipoprotein lipase (LPL), and LDL receptor] will be analyzed. We will determine the distribution of genetic variation within each ethnic group. We will also estimate the effects of genotype at each candidate gene locus on quantitative level of apolipoproteins and lipoproteins, and also on the degree and distribution of body fat after adjusting for concomitant variables (such as age, biologic maturation stage adiposity) within each ethnic group. By comparing the frequencies of genotypes at candidate loci, we will be able to assess their allelic effects and their impact on blood lipids and obesity development in black and white females. Thus, our study has the potential for identifying those genes which may be involved in determining black/white differences in lipid metabolism and obesity. This is an exciting area in which there is virtually no available information. Finally, our study will enable us to examine the effects of gene variation on changes in quantitative levels of blood lipids as well as in body fat during different stages of pubescence since the NGHS protocol includes annual anthropometric and maturation assessments and biannual blood lipid determinations along with extensive environmental measures which include dietary, household, and psychosocial information. Our study is a unique study because of the rare opportunity to do genetic analyses in a large cohort of 2 ethnic groups of children on whom a very rich data base is available. Thus, we have a rare opportunity to investigate in children: 1) the role of genotypes known to be associated with lipid metabolism and obesity; 2) the distribution of genetic variation in the 2 ethnic groups participating in the NGHS; and 3) the possible roles of specific genotypes on blood lipid and body fat changes during pubescence.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL045778-01A2
Application #
3364878
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1993-01-01
Project End
1995-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Hand, B D; McCole, S D; Brown, M D et al. (2006) NOS3 gene polymorphisms and exercise hemodynamics in postmenopausal women. Int J Sports Med 27:951-8
McCole, Steve D; Shuldiner, Alan R; Brown, Michael D et al. (2004) Beta2- and beta3-adrenergic receptor polymorphisms and exercise hemodynamics in postmenopausal women. J Appl Physiol 96:526-30
Hagberg, J M; McCole, S D; Ferrell, R E et al. (2003) Physical activity, hormone replacement therapy and plasma lipoprotein-lipid levels in postmenopausal women. Int J Sports Med 24:22-9
Moffett, Susan; Martinson, Jeremy; Shriver, Mark D et al. (2002) Genetic diversity and evolution of the human leptin locus tetranucleotide repeat. Hum Genet 110:412-7
McCole, Steve D; Brown, Michael D; Moore, Geoffrey E et al. (2002) Angiotensinogen M235T polymorphism associates with exercise hemodynamics in postmenopausal women. Physiol Genomics 10:63-9
Wilund, Kenneth R; Ferrell, Robert E; Phares, Dana A et al. (2002) Changes in high-density lipoprotein-cholesterol subfractions with exercise training may be dependent on cholesteryl ester transfer protein (CETP) genotype. Metabolism 51:774-8
Hagberg, James M; McCole, Steve D; Brown, Michael D et al. (2002) ACE insertion/deletion polymorphism and submaximal exercise hemodynamics in postmenopausal women. J Appl Physiol 92:1083-8
Hagberg, J M; Zmuda, J M; McCole, S D et al. (2001) Moderate physical activity is associated with higher bone mineral density in postmenopausal women. J Am Geriatr Soc 49:1411-7
Brown, M D; Shuldiner, A R; Ferrell, R E et al. (2001) FABP2 genotype is associated with insulin sensitivity in older women. Metabolism 50:1102-5
Hagberg, J M; Moore, G E; Ferrell, R E (2001) Specific genetic markers of endurance performance and VO2max. Exerc Sport Sci Rev 29:15-9

Showing the most recent 10 out of 14 publications