Relationship Between Coronary Heart Disease And DNA Polymorphisms Of Apolipoprotein B Gene (EcoRⅠ, MspⅠ And 3'VNTR) In Han Nationality

The gene of human apolipoprotein B(apoB) is located on the short arm of chromosome 2 at the p23~24 region and is 43 kilobase(kb) in length, with 28 introns and 29 exons. The mature RNA transcript of the apoB gene is 14kb and encodes 4536 amino acids. ApoB100 is the major protein component of chylomicrons(CM), very low density lipoprotein(VLDL), intermediate density lipoprotein(IDL), low density lipoprotein(LDL) and lipoprotein(a)[Lp(a)]. ApoB is involved in the assembly and secretion of both the CM from the small intestine and VLDL from the liver, and thus in the transfer of cholesterol and triglyceride in serum. Further, it functions as a ligand for the LDL-receptor and mediates the cellular uptake of cholesterol. Many epidemiological studies have shown that the high levels of apoB and LDL are important risk factors for premature atherosclerosis. Due to the central role played by apoB in the transport of lipids, it may be that genetic variations in the apoB gene could explain differences in serum lipid levels and susceptibility of individuals to coronary heart disease(CHD) reported in population studies.ApoB gene exists polymorphisms. Three common polymorphisms, EcoR I (exon 29) and Msp I (exon 26) and 3'VNTR(variable number of tandem repeats), have been associated with variation in lipid levels, CHD and myocardial infarction(MI). Msp I polymorphism in codon 3611 of the mature apoB protein is generated by G to A base transition, results in an amino acid change from arginine(CGG) to glutamine(CAG). On the other hand, the polymorphic region of EcoR I is caused by a base substitution(G→A) in the glutamine codon, resulting in a silent mutation, that changes glutamic acid(GAA) to lysine(AAA). 3'VNTR polymorphism is a hypervariable region(HVR) in the 3'end of apoB gene that comprises a minisatellite with 15 bases rich in A-T. Several studies have demonstrated that the association between apoB polymorphisms and high lipid levels are risk for CHD in some populations. However, these findings are not supported by other studies.