| Coronary heart disease (CHD) constitutes the major public health burden of industrialized nations. It also imperils the health of people in the developing countries. Due to the magnitude of the population in the developing countries, 80% of the death caused by CHD is in the developing countries and CHD is becoming one of the leading causes of death in China. The primary pathology of CHD is atherosclerosis and its progression is known to be influenced by risk factors such as cigarette smoking, elevated blood pressure, obesity, elevated serum LDL-C, and low serum HDL-C. Among the numerous risk factors low serum HDL-C is now generally accepted as a strong and independent risk factor for the CHD and it is influenced by many genetic and environmental factors. So it is urgent to find out CHD etiology and take effective prevention measures. To reach this target, a hospital-based molecular epidemiological study on CHD was conducted.Part I A Study on the Relationship between the Genetic Polymorphism of ATP-Binding Cassette transporter A and Susceptibility to Coronary Heart DiseaseABCAl mediates the movement of cholesterol from peripheral cells, including macrophage-derived foam cells in the arterial wall, back to the liver, where it is catabolized. This step is the first stage in reverse-cholesterol transport (RCT) and is important for the formation and maturity of HDL. Thus, ABCAl is the gatekeeper for cholesterol flux from tissues into the lipoprotein pathway-RCT. It is reported that ABCAl gene polymorphisms were suspected to be associated with plasma lipid levels and susceptibility to CHD. Thus, we evaluate the association between ABCAl R219K and M883I polymorphisms and host susceptibility to CHD.1, The distribution of genotypes of ABCAl in cases and controlsThe wild-type homozygote RR genotype frequencies of ABCAl R219K loci were 46.9% and 25.0%, respectively, in cases and controls, and the heterozygote RK genotype frequencies were 37.9% and 52.0% and the mutant-type homozygote KK genotype frequencies were 15.2% and 23.0%, respectively. The risks for CHD in those with 219KK genotype and 219RK genotype and 219RK+KK genotype were significantly lower than those with 219RR genotype, with an adjusted OR of 0.41 (95%CI= 0.24-0.72, 95%CI= 0.26-0.63, 95%CI= 0.27-0.61 respectively).The wild-type homozygote MM genotype frequencies of ABCAl M883I loci were 53.1% and 51.2%, respectively, in cases and controls,and the mutant-type homozygote II genotype frequencies were only 6.3% and 9.7%, respectively. Compared to MM genotype, only 883II homozygotes displayed a borderline significantly decreased risk for CHD (OR=0.54; 95%CI=0.25-1.13).Furthermore, the analysis of the combined effect of ABCAl R219K and M883I polymorphisms displayed that compared with individuals with both wild genotypes (219RR and 883MM or 883MI) other individuals with all other assembly genotypes had a significantly decreased risk for CHD (adjusted OR=0.39, 95%CI=0.26-0.60).2> A stratified analysis between ABCAl R219K polymorphism and risk factors on CHDIn a stratified analysis, significant differences were observed in terms of the associations between ABCAl R219K loci genotypes and CHD risk for female, non-smokers, high blood pressure sufferers, individuals with BMI>25kg/m2 and with HDL-C>1.04mmol/L.3, A stratified analysis between ABCAl R219K and M883I combined genotypes and risk factors on CHDIn a stratified analysis, significant differences were observed in terms of the associations between ABCAl R219K and M883I combined genotypes and CHD risk for female, non-smokers, high blood pressure sufferers, individuals with BMI>25kg/m2 and with HDL-C>1.04mmol/L.4, Association of the ABCA1 R219K polymorphism with plasma lipid levels in controlsHDL-C was significantly higher in the carriers of 219RK+KK genotype compared with carriers of 219RR genotype with an adjusted P value 0.037. No significant differences were detected between 219RK+KK genotype carriers and 219RR genotype carriers in other lipid levels. The lipid levels were not detected significant difference between... |
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