| BackgroundAldehyde dehydrogenase 2 (ALDH2) that influences alcohol consumption is the key enzyme in the process of ethanol elimination. Primarily, ALDH2 gene polymorphisms that resulted in the different activity of ALDH2 were discovered from the phenomenon that many Mongolian would flush after drinking alcohol while the Caucasians would not. With epidemiological studies indicating that drinking alcohol could cause many diseases, especially diabetes mellitus and myocardial infarction, researchers are drawing more and more attention to ALDH2 gene polymorphisms. Murata's research showed that inactive ALDH2 worsen glycemic control in patients with type 2 diabetes mellitus who drank low to moderate amounts of alcohol, but the relationship between ALDH2 gene polymorphisms and diabetes mellitus was still unclear. While Takagi discovered that the mutant allele of ALDH2 could be a high risk factor for myocardial infarction in Japanese men, Narita's research indicated that it would protect the artery from atherosclerosis. The role and mechanism of ALDH2 gene polymorphisms in coronary atherosclerosis still remained controversial.Objectives1. To investigate the association between aldehyde dehydrogenase 2(ALDH2) gene polymorphisms and type 2 diabetes mellitus (T2DM) in Chinese Han patients with coronary heart disease.2. To evaluate the mutual influences of ALDH2 gene polymorphisms and alcohol consumption on the prevalence of T2DM.3. To assess the relationship between ALDH2 gene polymorphisms and the severity of coronary atherosclerosis.MethodsTo execute the project, we adopt the method of case-case study. Two hundred and thirty-one Chinese Han patients with coronary heart disease who underwent coronary angiography (CAG) in our hospital were accumulated from December. 2005 to September. 2006. The clinical data were collected using the structured questionnaire, with the Gensini score which showed the severity of coronary atherosclerosis calculated by two skilled doctors referencing the pictures of CAG. The ALDH2 genotypes were examined by gene sequencing. Patients were divided into two groups according to their ALDH2 genotypes: wild genotype (n=145) and mutant genotypes (n=86). Statistically compare the differences of clinical data including the prevalence of T2DM and the Gensini score between the two groups. Evaluate the mutual influences of ALDH2 gene polymorphisms and alcohol consumption on the prevalence of T2DM in the logistic model.ResultsThe prevalence of T2DM and Flushing reaction was higher in the mutant ALDH2 genotypes group than in the wild genotype group (P<0.01), but the alcohol consumption was lower. While the prevalence of MI was significantly higher in the mutant ALDH2 genotypes group than in the wild genotype group (P<0.01), the Gensini score which embody the severity of coronary atherosclerosis was almost same between the two groups, and the other basic clinical data were also similar. After adjustment for age, smoking, triglyceride and hypertension using a multi-variable logistic regression, the odds ratio (OR) of the risk of T2DM for the mutant genotypes compared with the wild genotype was 6.08(P=0.004), and the inclusion of alcohol consumption as one independent variable did not affect the relationship between ALDH2 genotypes and T2DM(OR=5.73, P=0.008). Conclusions1. The mutant allele of ALDH2 is associated with a high risk for T2DM among Chinese Han patients with coronary heart disease.2. ALDH2 genotypes act on T2DM not by alcohol consumption, probably by some independent mechanism, although it influences on alcohol consumption.3. ALDH2 genotype is associated with the prevalence rate of myocardial infarction, however, not with the severity of coronary atherosclerosis.
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