Association Of NAD(P)H Oxidase P22phox Gene A640G Mutation And Coronary Heart Disease

BackgroundCoronary heart disease (CHD), a kind of cardiovascular disease, does great harm to our health and the quality of life. The prevalence increases rapidly in recent years in the world, which has been a severe problem of public health in our country as well as in many other countries. For this reason, exploring the pathogenic mechanism and the risk factors of CHD may be meaningful theoretically and practically for identifying high risk population and providing information for prevention and treatment.CHD is a multi-factorial disease influenced by both genetic and environmental factors. The gene-gene, gene-environment interactions make a great contribution to the onset of CHD. The role of environmental factors in the pathogenesis of CHD has been confirmed by a large number of researches. Recently, the development of molecular biology technique provides techniques and conditions to study the pathogenesis of CHD at the molecular level.Excessive reactive oxygen species (ROS)and/or imbalance of antioxidant defense system in vivo can disorder the structure and function of vascular endothelial, resulting in the occurrence and development of atherosclerosis. NAD (P) H oxidase is the major source of reactive oxygen species in the vascular wall. P22phox is a critical component of the NAD(P)H oxidase system and plays an important role in electron transport and superoxide anion production (the major source of ROS in the vasculature). The association of A640G polymorphism and coronary artery disease has been studied in several different ethnic groups with conflicting results. However, there are not similar study reports in China. The dominant study is mainly between the relationship of p22phox gene A640G mutation and diabetes and is not reflected with coronary heart disease. So we perform a case-control study to detect if there is any effect between p22phox gene A640G mutation and CHD, and assess the interaction between the mutation and the other risk factors on premature CHD.Objectives1. To detect the association between p22phox gene A640G mutation and coronary heart disease;2. To assess the interaction between p22phox gene A640G mutation and other risk factors on premature coronary heart disease.MethodsHospital based case-control study was used.898 newly-diagnosed CHD patients were chosen as patients and 347 health persons who came to the Physical Examination Center for a medical checkup were selected as the controls. In order to detect the relationship between p22phox gene A640G mutation and CHD in different age groups, we divided the patients into two groups:the 421 premature CAD group diagnosed at or before age 55 for male and 65 for female and other 477 late-onset CAD. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to detect the p22phox A640G polymorphism.Univariate and multivariate logistic regression models were performed to explore the effect of p22phox gene A640G mutation on premature CHD and late-onset CHD. Additive model was applied to assess the interaction between p22phox gene A640G mutation and overweight, hypertension and smoking consumption separately on premature CHD. Results1. There was no statistically significant association between p22phox gene A640G mutation and CHD. The G allele frequency in premature CHD group, late-onset CHD and control group were 63.64%,64.62% and 65.02% separately, which were not significantly different among the three groups, and the result was the same in female after stratifying by gender, with 62.01%,63.56% and 64.52% in G allele frequency in premature CHD group, late-onset CHD and control group separately. Also, there was no significant effect of the p22phox gene A640G mutation on CHD after adjusting several confounding factors by analysis of multiple covar(?)ances.2. There was no statistically significant interaction between p22phox gene A640G mutation with overweight, hypertension and smoking consumption separately on premature CHD; the results were the same after adjusting several confounding factors by analysis of multiple covariance.(1) In the analysis of interaction between p22phox gene A640G mutation and overweight, the synergy index was 0.347(95%CI:0.115-1.042) in univariate analysis and 0.371(95%CI:0.126-1.091) after adjusting sex, age, smoking, alcohol drinking, hypertension, total cholesterol, and triglyceride in logistic regression. The results suggest that there is no interaction between p22phox gene A640G mutation and overweight on premature CHD.(2) In the analysis of interaction between p22phox gene A640G mutation and hypertension, the synergy index was 1.010 (95%CI:0.258-3.963) in univariate analysis and 1.618 (95%CI:0.384-6.811) after adjusting sex, age, smoking, alcohol drinking, overweight, total cholesterol, and triglyceride in logistic regression. The results suggest that there is no interaction between p22phox gene A640G mutation and hypertension on premature CHD.(3) When it comes to the interaction between p22phox gene A640G mutation and smoking, the synergy index was-0.606 in univariate analysis and 1.383(95%CI: 0.488-4.275) after adjusting sex, age, alcohol drinking, hypertension, total cholesterol, and triglyceride in logistic regression. The results suggest that there is no interaction between p22phox gene A640G mutation and smoking on premature CHD.Conclusions1. The p22phox gene A640G mutation may not a major factor in CHD in this studied population.2. There was no statistically significant interaction between p22phox gene A640G mutation with overweight, hypertension and smoking consumption separately on premature CHD.