The long term objectives of this proposal are to study two well defined African populations from Nigeria to determine the contribution of 14 polymorphic genes involved in lipid metabolism in determining quantitative lipoprotein-lipid and apolipoprotein levels as these are major risk factors for coronary hear disease, and to investigate how differences in life styles and dietary habits modulate the genetic contribution on these quantitative risk factors. Phenotypes in the gene products of APOs A-IV, C-II, D, H, J and (a) will be determined by IEF and SDS/immunoblotting and genotypes at the B,E, AI-CIII- AIV cluster, lipoprotein lipase, hepatic lipase, LDL-receptor, and cholesterol ester transfer protein will be determined by polymerase chain reaction protocols. The quantitative levels of total cholesterol, HDL-cholesterol and its subfractions, HDL2- and HDL3-cholesterol, triglycerides and LP(a) will be used in the genetic analyses. Estimates of the effect of alleles at each of the candidate loci on quantitative lipoprotein-lipid levels will employ the measured genotype approach. The effect of multisite haplotypes for RFLP at various loci, where applicable, will also be estimated using the same method. The interaction of alleles at various independent loci in determine quantitative lipoprotein-lipid and apolipoprotein levels will be estimated. In addition to the measurements of environmental effects, we will also measure the genotype-environmental interaction in determining quantitative risk factor traits.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL049074-01A2
Application #
2225152
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1994-04-01
Project End
1998-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Genetics
Type
Schools of Public Health
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Nestlerode, C S; Bunker, C H; Sanghera, D K et al. (1999) Apolipoprotein J polymorphisms and serum HDL cholesterol levels in African blacks. Hum Biol 71:197-218
Kamboh, M I; Bunker, C H; Aston, C E et al. (1999) Genetic association of five apolipoprotein polymorphisms with serum lipoprotein-lipid levels in African blacks. Genet Epidemiol 16:205-22
Sanghera, D K; Saha, N; Kamboh, M I (1998) The codon 55 polymorphism in the paraoxonase 1 gene is not associated with the risk of coronary heart disease in Asian Indians and Chinese. Atherosclerosis 136:217-23
Sanghera, D K; Aston, C E; Saha, N et al. (1998) DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease. Am J Hum Genet 62:36-44
Harris, M R; Bunker, C H; Hamman, R F et al. (1998) Racial differences in the distribution of a low density lipoprotein receptor-related protein (LRP) polymorphism and its association with serum lipoprotein, lipid and apolipoprotein levels. Atherosclerosis 137:187-95
Ali, S; Bunker, C H; Aston, C E et al. (1998) Apolipoprotein A kringle 4 polymorphism and serum lipoprotein (a) concentrations in African blacks. Hum Biol 70:477-90
Kamboh, M I; Sanghera, D K; Aston, C E et al. (1997) Gender-specific nonrandom association between the alpha 1-antichymotrypsin and apolipoprotein E polymorphisms in the general population and its implication for the risk of Alzheimer's disease. Genet Epidemiol 14:169-80
Sanghera, D K; Saha, N; Aston, C E et al. (1997) Genetic polymorphism of paraoxonase and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol 17:1067-73
Anderson, J L; Bunker, C H; Aston, C E et al. (1997) Relationship of two apolipoprotein B polymorphisms with serum lipoprotein and lipid levels in African blacks. Hum Biol 69:793-807

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