ENOS Intron 4 VNTR Polymorphisms And Environmental Factor Exposure In Premature Coronary Heart Disease

Background: Coronary heart disease (CHD), as a kind of cardiovascular disease, does great harm to the human health and the quality of life. According to World Health Report 2003, coronary vascular disease (CVD) made up 16.7 million, or 29.2% of total global deaths. Around 80% of CVD deaths took place in low and middle-income countries. By 2010, CVD will be the leading cause of death in developing countries. At least 20 million people survive heart attacks and strokes every year; many require continuing costly clinical care. Heart disease has no geographic, gender or socio-economic boundaries. In China, the incidence and mortality rate of CHD has been going up year by year since 1980. From the statistic center's information of the ministry of health, among first ten principle diseases constitute of City dweller in 2005, heart disease is the third just following the malignancy and the cerebrovascular disease (CVD), the mortality was 53.42 per a hundred thousand persons, and the mortality of Country dweller was 49.40 per a hundred thousand persons, which was the fourth of the first ten death causes.CHD is multifactorial disease influenced by both genetic and environmental factors. The Gene-gene, gene-environment interaction makes a great contribution to the risk of CHD. According to recent years' reports, arguments still existed about the relation between the eNOS4a/bVNTR polymorphisms and premature CHD (p-CHD); meanwhile, there are few reports about the relationship between the gene mutation and the other risk factors of p-CHD.Objective: To explore the association between the eNOS4 VNTR polymorphisms and the p-CHD; to analyze the relation between the eNOS4 VNTR polymorphisms and the risk factors of CHD; to study the major risk factors and major high risk population of p-CHD by the Classification Tree.Methods: A hospital-based case-control study was conducted. Newly-diagnosed CHD patients were recruited as study subjects. 188 CHD patients diagnosed at / before 55 for males and 65 for females were assigned to p-CHD case group with other 315 CHD patients as the control group. Genotypes were detected by polymerase chain reaction (PCR) technique. The univariate analysis and logistic regression model were applied to analyze the association between eNOS4 VNTR polymorphisms and p-CHD and explore the relation between the eNOS4a gene mutation and the other risk factors of CHD; the Classification Tree was performed to study the major risk factors and major high risk population for p-CHD.Results:1. The eNOS4a/b VNTR polymorphisms were not associated with the p-CHD. There was no significant difference of the eNOS4a allele frequency between the p-CHD group(9.84%) and the control group(12.06%); there was no significant difference of the eNOS4(a/a+a/b) genotype frequency between the p-CHD group(18.09%) and the control group(22.22%); At 0.05 significant level with gender, smoking, alcohol drinking, systolic blood pressure, diastolic blood pressure, overweight, serum triglyceride, serum total cholesterol as the covariates, multivariate logistic regression analysis showed that the eNOS4a also had no significant effect on p-CHD. So the mutation gene eNOS4a was not the risk factor for the p-CHD.2. The relationship between the eNOS4a/b VNTR polymorphisms and the other risk factors of the p-CHDBoth in the p-CHD and control groups, there was no significant difference of the body mass index, systolic blood pressure, diastolic blood pressure, triglyceride and total cholesterol levels in the carriers with genotype eNOS4(a/a+a/b) and the eNOS4b/b.Both in the p-CHD and control groups, no significant associations were found between the eNOS4a and smoking, alcohol drinking, hypertension (HT), overweight or obesity, high triglyceride and high cholesterol.3. In the order of contribution to p-CHD from big to small in the Classification Tree analysis, the major classification variables were the family history of the CHD, HT and CVD, gender, body mass index, alcohol drinking, total cholesterol, smoking, eNOS4a/b gene mutation. The major high risk people were that:â‘ people who had positive family history of CHD, HT and CVD, and alcohol drinking;â‘¡people whose triglyceride was more than 3.60mmol/L;â‘¢people who had positive family history of CHD, HT and CVD, female and BMI higher than 19.673 Kg/m~2;â‘£people who had positive family history of CHD, HT and CVD, male, smoking and total cholesterol more than 4.04mmol/L. The classification table made clear that the sensitivity of the model was 69.1%, the specificity was 75.9%, and the correct classifying ratio of the model is 73.4%.Conclusions:1. The mutation gene eNOS4a was not the major risk factor for p-CHD in the studied population.2. There was no association between the eNOS4a/b polymorphisms and the other risk factors for p-CHD (smoking, alcohol drinking, hypertension, overweight, triglyceride and total cholesterol).3. The p-CHD has different types of high risk population. It should be taken into account, during the medication, prevention and control of p-CHD.