In Vivo Human Study On The Relationship Between ALDH2Gene Polymorphism And Onset Time Phase Efficacy Of Nitroglycerin In Patients With Coronary Heart Disease (CHD) Sublingual Administration

ObjectiveCoronary atherosclerotic heart disease (coronary heart disease, CHD) is the most common cause of atherosclerosis in type of organ lesions, it is also a common disease that damages human health.Nitroglycerin is commonly used for the treatment of angina pectoris. But because of the effect of individual difference among different patients,resulting in patients taking nitroglycerin can not effectively alleviate the symptoms of chest pain. At present, the individual of aldehyde dehydrogenase2gene polymorphism may be one of the reasons of individual differences and racial differences in pharmacodynamic.This paper aims to investigate the relationship between aldehyde dehydrogenase-2(ALDH2) gene polymorphisms and onset time phase efficacy of nitroglycerin in patients with CHD sublingual administration.MethodFour hundred and ninety CHD patients who were confirmed by coronary angiography (one of the main coronary arteries narrows≧50%)were involved in this study. We obtained the DNA from2ml peripheral blood of each patient. Polymerase Chain Reaction(PCR)and reverse direct sequencing were performed to screen the polymorphism of ALDH2gene in exon12.The whole patients were divided into two groups according to the ALDH2Gene Polymorphisms:Group A (GG gene),n=240and Group B (GA/AA genes),n=250. Application of Impedance CardioGraphy (ICG) were measured in two groups of subjects before treatment (Omin) and medication after different time points (3min,6min,9min,12min,15min) of ICG index CI (cardiac index) and LCWI (left ventricular work index), and analysis the change of the two groups of ICG index. The data were analyzed by SPSS17.0, were compared between groups using independent sample t test or variance, within group compared with the SNK-q test. Count data using Pearson chi square test (χ2)Result1.490subjects genotype distribution conforms to the Hardy-Weinberg law of genetic equilibrium(χ=2.463,P>0.05),the results showed that the sample has a population representative. There were no significant differences between the two groups in gender, age, smoking, alcohol drinking habit (P>0.05).2.the CI and LCWI changes within wild type and mutant type:in mutant group CI, LCWI (3min,6min in Omin,9min,12min,15min) had significant difference between the six time points (P=0.018, P=0.004); the wild group CI, LCWI were significantly different in the six time points (P=0.01, P=0.000).3.ICG index of CI and LCWI changes between the two groups:ACI1=CI0min-Cl3min, ACl2=CI0min-Cl6min,△CI3=CI0min-Cl9min,△CI4=CI0min-CI12min,CI5=CI0minCI15min,△LCWI1=LCWI0min-LCWI3min,ALCWI2=LCWI0min-LCWI6min, LCWI3=LCWI0min-LCWI9min,LCWI4=LCWI0min-LCWI12min, LCWI5=LCWIomin-LCWI15min.Comparison of wild-type and mutant on A CI1,△LCWI1was statistically significant (P<0.001,P<0.001);Similarly, the comparison between wild type and mutant type on△CI2△LCWI2;△CI3△LCWI3;△CI4△LCWI4;△CI5,△LCWI5were statistical significant (P<0.001)ConclusionThe genotype of G/A polymorphism in aldehyde dehydrogenase-2(ALDH2) gene is associate with the Onset Time Phase Efficacy of Nitroglycerin in Patients with CHD sublingual administration.