Study Of Point Mutations Of Low Density Lipoprotein-Receptor And Apolipoprotein B, Two Major Genes Related To Metabolism Of Low Density Lipoprotein Cholesterol

Coronary heart disease(CHD) is a common disease harming human health severely. It is a kind of multigenetic disease caused by genetic factors and environmental factors. Many risk factors for CHD have now been identified. Among them, the three most important ones are abnormal lipids, high blood pressure, and cigarette smoking. In dyslipidemia, high level of low density lipoprotein cholesterol(LDL-C) is strongly related to CHD.Low density lipoprotein receptor(LDL-R) and apolipoprotein B(apo B) are two major factors participating in metabolism of LDL-C. Abnormality in genetic structure and expression is the ultimate reason of disease, and gene mutation is the common mechanism. To probe into the etiological mechanism of dyslipidemia at molecular level and enhance the development of molecular cardiovasology, we studied the point mutations of LDL-R and apo B using a series of advanced techniques of molecular biology. The study is focused mainly on the two parts.I. Study of point mutations of LDL-R gene in familial hypercholesterolemic patientsFamilial hypercholesterolemia(FH), an important risk factor of CHD, is caused by mutations in the gene for LDL-R. In FH patients, plasma LDL-C concentration is elevated due to dysfunction of LDL-R protein. FH is an autosomal dominant disorder with a heterozygote frequency of 1/500. Homozygous FH patients are fortunately rare,...