| BackgroundThe full name of CHD is coronary heart disease (coronary heart disease CHD), which is a kind of cardiomyopathy caused by cardiac insufficiency or interruption because of coronary stenosis or occlusion as a result of coronary atherosclerosis or spasm, also known as ischemic heart disease. CHD has become one of the major reasons of death and disability globally. According to the report of World Health Organization in 2000, there are 17 million people died from cardiovascular diseases ,out of every three people dead, one died of cardiovascular diseases. By 2020 this figure is expected to increase by 50% and 80% of the deaths distribute in low-and middle-income countries. From 2000 to 2020, myocardial infarction in the various causes of death will rise from the fifth place to the first. Being called "the first killer of human health" , cardiovascular diseases has become the first cause of death in China, of which coronary heart disease is the most important one. According to statistics, in every 100 Chinese aged over 40 there are 4-7 patients suffering from coronary heart disease. At present, the number of people died of various coronary heart diseases is more than 1 million in China's mainland each year, with a relatively rapid rise in morbidity and mortality ; the onset age becomes more and more younger, and the mortality in 35 to 55-year-old male coronary heart disease patients increases most rapidly. The etiology of this disease is not entirely clear, a large number of studies show that the disease is caused by many factors, which are called risk factors: dyslipidemia, smoking, drinking, hypertension, diabetes, genetic factors, age , sex, obesity and so on. Among them, type 2 diabetes mellitus (T2DM) being a great risk of coronary heart disease has become a consensus. The results of the China cardiac survey show that in patients with coronary heart disease, almost 80% have an abnormal glucose increase, of which 53 percent are Type 2 diabetes, 24 percent are pre-diabetes. Alcohol dehydrogenase (ADH) is one of the key enzymes in the metabolism of alcohol, whose function is to oxidize ethanol into acetaldehyde. ADH is a kind of zinc metal, with more than 20 kinds of isozymes, of which ADH1 - ADH5 are common ones. Study has found that only ADH2 and ADH3 have polymorphism loci. The study of ADH isozymes dynamics found that the two isozymes encoded by ADH3 gene have a little difference in ethanol Km values, and the difference is only in the Vm values of 2.5 times. The differences of ADH isoenzyme activity should be attributed to the ADH2 gene loci polymorphism. The distribution frequency of ADH2 gene mutation has an ethnic difference, and it is reported that there are significant differences between Japanese, Chinese, African-Americans and Brazilians. A foreign epidemiological survey found that alcohol level and type 2 diabetes prevalence rate have a "U"-typed relation. So far the relationship between ADH2 gene polymorphism in CHD patients and type 2 diabetes onset has not been reported. Therefore, to study the relationship of ADH2 gene polymorphism in Han patients with coronary heart disease and type 2 diabetes will help to identify the high-risk groups of patients with coronary heart disease to prevent or delay the occurrence of type 2 diabetes mellitus.Reasearch objective(1) the realationships between ADH2 polymorphism in CHD patients and T2DM(2) the effect mechanism of ADH2 polymorphism in CHD patients to T2DMResearch design and methodsThe study subjects were 227 patients who visited the Qilu Hospital with defined coronary heart disease, including acute myocardial infarction 53 cases, unstable angina pectoris 154 cases and chronic stable coronary heart disease 20 cases. The subjects comprised 63 females and 164 males, with mean age 61.7+10.4 years. Its clinical manifestations and ECG conformed to the 1979 WHO diagnostic criteria for coronary heart disease, with at least one narrow, and > 50% (diameter) by coronary angiography.Take 2 ml arterial blood with sodium citrate anticoagulation. Abstract DNA from the blood. Design specific primers for the target DNA fragments, then go on PCR. Electrophoresis amplified products in the 2% agarose gel, divide the subjects into the wild-type group and the mutant group according to electrophoresis results. Inquire and collect the subjects' detailed information about the disease: age, sex, hypertension, T2DM, family history of cardiovascular disease, face-reaction after drink, smoking, history of alcohol , waist circumference and other basic information. Take early morning blood (fasting for 10 hours), then measure fasting glucose, glycosylated hemoglobin (HbAlc), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C); account the alcohol volumn through inquisition.Use SPSS11.5 statistical software packages for data analysis, x±s for numerical variables and frequency for classification variables . t-test are used in comparison of numerical variables and x~2 in classification variables. Use multi-factor logistic regression to correcte age, hypertension, TG, smoking, family history of cardiovascular disease and other factors. Approach the relationship between ADH2 genotypes in CHD patients and the T2DM prevalence. That P <0.05 shows a statistical significance.Results21.1 percent of the subjects have a history of type 2 diabetes. The number of CHD patients with wild-type group of ADH2 genes is 102 cases, and with mutant-type group is 125 cases. 39.2 percent of patients with CHD in the wild-type group have T2DM, significantly higher than 6% of the mutate-type group (P<0. 01). Logistic multiple regression analysis shows that ADH2 genotype and T2DM were more relevant (P< 0.01).For subjects without a history of T2DM, the level of BMI, waist circumference, serum total cholesterol, LDL-C, triglyceride increases as HbAlc quartile numerus increases. Logistic multiple regression analysis shows that HbAlc and BMI, waist circumference, serum total cholesterol, TG, LDL-C were more relevant(P<0.01).The level of HbAlc is 5.51%±0. 4%, 5. 92%±0. 4% and 6. 41%±0. 5% respectively in the patients with chronic stable CHD,unstable angina pectoris and acute myocardial infarction. There is a statistical significance between the three groupes (P<0. 05).Conclusions1. Most coronary heart disease risk factors such as age, BMI, waist circumference, serum total cholesterol, LDL-C, triglycerides have a strong positive correlation with HbAlc. The CHD patients with high blood HbAlc levels have higher levels of morbidity. Therefore, HbAlc may be involved in the atherosclerosis process, and closely related to coronary heart disease.2. T2DM prevalence rate in wild-type group is higher than that in mutant-type group, and there is an obvious gap in alcohol level between the two groups. Although the level of alcohol may contribute to the effect of the ADH2 genotype to T2DM, but its effect is very small. The effect of the ADH2 polymorphism in CHD patients to T2DM has a unique mechanism. |
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