The overall goal of this project is to understand the genetic epidemiology of coronary heart disease (CHD) risk factors in Japanese- American families with probands living in Seattle, Washington. These risk factors are: low-density lipoprotein (LDL) subclass phenotypes (denoted atherogenic lipoprotein phenotypes (ALP)); the risk factors that characterize the insulin resistance syndrome and non-insulin-dependent diabetes (NIDDM); and lipoprotein(a) (Lp(a)) plasma levels and apolipoprotein(a) phenotypes. Although each of these risk factors have recently been associated with increased risk of CHD and are known to be genetically influenced, none of them have been investigated in a large sample of American families of Japanese ancestry.
The specific aims are: 1) To test the hypothesis that a predominance of small LDL particles (ALP phenotype B), as determined by gradient gel electrophoresis, is inherited as a single gene trait in Japanese-American kindreds using complex segregation analysis; to compare these results with previous studies in Caucasian families; and to test the hypothesis that ALP-B is associated with risk factors characteristic of the insulin resistance syndrome and NIDDM among individual Japanese-American family members. 2) To test the hypothesis that plasma levels of Lp(a) are inversely associated with apo(a) size phenotypes, as determined by high- resolution SDS-agarose-gel electrophoresis followed by immunoblotting, in individual Japanese-American subjects, and to compare and contrast these associations with those previously reported in Caucasians and other ethnic groups; to test the hypothesis that in addition to apo(a) gene effects, the segregation of plasma levels of Lp(a) in families in inherited consistent with the presence of another single major gene effect. 3) To establish a repository of frozen white cells for future genetic studies of candidate genes associated with risk of CHD in Japanese Americans. These hypotheses will all be tested based on blood samples, blood pressure and anthropometric measurements, and questionnaire data from 33 Japanese-American kindreds identified through participants in the ongoing Japanese-American Community Diabetes Study in Seattle. The kindreds consist of 126 nuclear families and 443 individual family members, including probands, siblings, spouses, offspring and nieces and nephews of full Japanese descent. This project represents a unique and timely opportunity to characterize the genetic epidemiology of CHD risk factors among Japanese Americans. The findings could lead to the development of effective preventive strategies targeted to subgroups of individuals with high risk due to underlying genetic susceptibility.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL050268-02
Application #
2226405
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1994-01-01
Project End
1997-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Pierce, Brandon L; Austin, Melissa A; Crane, Paul K et al. (2007) Measuring dietary acculturation in Japanese Americans with the use of confirmatory factor analysis of food-frequency data. Am J Clin Nutr 86:496-503
Hutter, Carolyn M; Austin, Melissa A; Farin, Federico M et al. (2006) Association of endothelial lipase gene (LIPG) haplotypes with high-density lipoprotein cholesterol subfractions and apolipoprotein AI plasma levels in Japanese Americans. Atherosclerosis 185:78-86
Austin, M A; Zhang, C; Humphries, S E et al. (2004) Heritability of C-reactive protein and association with apolipoprotein E genotypes in Japanese Americans. Ann Hum Genet 68:179-88
Austin, Melissa A; Talmud, Philippa J; Farin, Federico M et al. (2004) Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans. Biochim Biophys Acta 1688:1-9
Austin, Melissa A; Edwards, Karen L; McNeely, Marguerite J et al. (2004) Heritability of multivariate factors of the metabolic syndrome in nondiabetic Japanese americans. Diabetes 53:1166-9
Austin, M A; Rodriguez, B L; McKnight, B et al. (2000) Low-density lipoprotein particle size, triglycerides, and high-density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese-American men. Am J Cardiol 86:412-6
Austin, M A (1996) Genetic epidemiology of dyslipidaemia and atherosclerosis. Ann Med 28:459-63