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.
