Association between eNOS and ACE Genetic Polymorphisms and the Therapeutic Efficacy of Salvianolate Injection in Coronary Heart Disease Patients
|School||Central South University|
|Keywords||endothelial nitric oxide synthase angiotensin convertingenzyme gene polymorphism coronary heart disease salvianolateinjection|
Objective:The purpose of this study is to clarify the distribution of eNOS894G/T and ACE I/D genetic polymorphisms in Chinese Han population and to explore the effect of eNOS and ACE gene polymorphism on the response to salvianolate in patients with CHD.Methods:In this study we selected153cases of non-ischemic cardiomyopathy and non-sudden death in patients with coronary heart disease and compared with198healthy controls. We collected5ml peripheral blood to extract DNA. Genetic diagnosis of eNOS894G/T was determined by direct sequencing. Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used to detect the genotypes in ACE I/D. Clinical characteristics of CHD patients and healthy controls were compared using the Chi-square test. Independent-Sample Test, One-Way ANOVA, Chi-square test and Binary logistic regression were used for statistical analysis of genetic parameters.Results:By genotyping the selected153cases of coronary heart disease patients and198healthy controls for eNOS894G/T and ACE I/D, we observed that,(1) there were significant differences in the frequency distribution of eNOS and ACE polymorphisms between CHD patients and healthy controls (T allele:16.01%vs10.61%, I allele:55.56%vs45.86%; p<0.05).(2) there are significant differences in plasma ApoAl-C between the eNOS G894T genotypes (p<0.05). Meanwhile there are edge statistical differences in plasma TC and LDL cholesterol levels between ACE genotypes(p=0.078and0.063).(3) Binary logistic regression analysis revealed that the genotypes had an additive and dominant effect on patients’therapeutic response (T/T and G/T vs G/G, odds ratio:2.401, p=0.032, I/I vs I/D vs D/D, odds ratio:1.738, p=0.013; T/T and G/T vs G/G, odds ratio:2.446,p=0.028, D/D and I/D vs I/I, odds ratio:2.414, p=0.015)Conclusion:The gene polymorphisms of eNOS gene894G/T and ACE I/D are related to the occurrence of coronary heart disease. These data suggest that genetic variations in eNOS and ACE might affect the response to salvianolate in Chinese CHD patients. Patients carrying eNOS894G or ACE D alleles are good responders to salvianolate therapy.