Grant: China-Canada Joint Health Research Initiative

PCSK9 is a protein released into blood by the liver. Its function is to limit the uptake of blood cholesterol by liver cells. There are many heritably altered forms of this protein caused by mutations in its gene: some rare forms restrict the cholesterol uptake too stringently, causing an increase in blood cholesterol, a risk factor for cardiovascular disease (CVD); other relatively more frequent forms allow greater uptake, causing a drop in blood cholesterol and thus reducing the risk of CVD. Interestingly, the nature and the occurrence of these altered forms of PCSK9 differ by ancestries. They have not been systematically investigated in populations of Chinese descent. The goal of this research is to determine (i) which altered forms of PCSK9 are found in Chinese living in Changhai and in Ontario; (ii) how these forms influence blood cholesterol levels. We will search for mutations in the PCSK9 gene in DNA from donors. We will examine whether or not these mutations tend to cluster in individuals with blood cholesterol below or above normal range. We will then attempt to explain the observed clustering by analyzing how the mutations affect cholesterol metabolism in cultured cells. Relative to Caucasians, Chinese are prone to certain forms of CVD such as stroke, but less so to others such as coronary heart disease. This study may provide some explanation for this differential susceptibility. In addition, it may offer opportunities of ethnicity-based screening for CVD risk factor for the purpose of prevention and treatment in China and in Canada.