Our overall objective is to understand the role of apolipoprotein B and apolipoprotein A1 in the etiology of coronary artery disease (CAD).
Our specific aims are: 1) Using our previously characterized population of 200 index cases (100 men, 100 women) who underwent elective coronary arteriography at the Johns Hopkins Hospital, we propose to determine if the apolipoprotein B gene and apolipoprotein A1-C3-A4 gene cluster are independent predictors of CAD. Using cloned DNA fragments as molecular probes, the relation between DNA polymorphic sites within these two genes and CAD will be determined after other risk factors have been considered. Based on studies in first degree relatives of the index cases, haplotypes of DNA polymorphisms will be assigned and their association with CAD studied. 2) To determine if apolipoprotein B and apolipoprotein A1 levels aggregate in families and explain a significant proportion of the positive family history of CAD and to determine if hyperapo B and hypoalphalipoproteinemia segregate as Mendelian traits. Age adjusted and sex specific cut points derived from the Columbia population (100 males, 100 females) will be used to define hyperapoB and hypoalphalipoproteinemia in the 200 index cases and their first degree relatives (N = 900). Through genetic analysis of both apolipoprotein levels and lipoprotein phenotypes, we will test for genetic control of apolipoprotein B and apolipoprotein A1 levels. 3) To determine if there is linkage between a) hyperapoB and haplotypes of the apolipoprotein B gene; b) hyperapoB and the Ag polymorphisms; c) hypoalphalipoproteinemia and haplotypes of the apolipoprotein A1-C3-A4 gene cluster; and to study genetic defects in the apolipoprotein B gene and the apolipoprotein A1-C3-A4 gene cluster. These studies may improve our understanding of the pathophysiology of CAD, of the genetic and biochemical defects of hyperapoB and hypoalphalipoproteinemia and may explain a significant proportion of the risk of developing CAD that is currently poorly understood.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031497-08
Application #
3342667
Study Section
Metabolism Study Section (MET)
Project Start
1984-08-01
Project End
1992-07-31
Budget Start
1991-08-09
Budget End
1992-07-31
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Juo, S H; Beaty, T H; Duffy, D L et al. (1999) No common major gene for apolipoprotein A-I and HDL3-C levels: evidence from bivariate segregation analysis. Genet Epidemiol 16:54-68
Kwiterovich Jr, P O; Motevalli, M (1998) Differential effect of genistein on the stimulation of cholesterol production by basic protein II in normal and hyperapoB fibroblasts. Arterioscler Thromb Vasc Biol 18:57-64
Juo, S H; Beaty, T H; Xu, J et al. (1998) Segregation analysis of two-locus models regulating apolipoprotein-A1 levels. Genet Epidemiol 15:73-86
Juo, S H; Beaty, T H; Kwiterovich Jr, P O (1997) Etiologic heterogeneity of hyperapobetalipoproteinemia (hyperapoB). Results from segregation analysis in families with premature coronary artery disease. Arterioscler Thromb Vasc Biol 17:2729-36
Kwiterovich Jr, P O (1995) Detection and treatment of elevated blood lipids and other risk factors for coronary artery disease in youth. Ann N Y Acad Sci 748:313-30;discussion 331-2
Kwiterovich Jr, P O; Motevalli, M (1995) Inhibition of protein tyrosine kinase alters the effect of serum basic protein I on triacylglycerols and cholesterol differently in normal and hyperapoB fibroblasts. Arterioscler Thromb Vasc Biol 15:1195-203
Coresh, J; Beaty, T H; Prenger, V L et al. (1995) Segregation analysis of HDL3-C levels in families of patients undergoing coronary arteriography at an early age. Arterioscler Thromb Vasc Biol 15:1307-13
Kwiterovich Jr, P O; Motevalli, M; Miller, M (1994) The effect of three serum basic proteins on the mass of lipids in normal and hyperapoB fibroblasts. Arterioscler Thromb 14:1-7
Kwiterovich Jr, P O (1994) Dyslipoproteinemia and other risk factors for atherosclerosis in children and adolescents. Atherosclerosis 108 Suppl:S55-71
Coresh, J; Beaty, T H; Kwiterovich Jr, P O (1993) Inheritance of plasma apolipoprotein B levels in families of patients undergoing coronary arteriography at an early age. Genet Epidemiol 10:159-76

Showing the most recent 10 out of 34 publications