ALDH2 genetic polymorphism and the risk of type II diabetes mellitus in CAD patients.

The prevalence of type II diabetes mellitus (T2DM) in coronary artery disease (CAD) patients has been steadily increasing, especially in East Asian countries. Although many studies have suggested that certain genetic variants may predispose to the development of T2DM, very few studies investigated the genetic link with T2DM in CAD patients of East Asia. In this study, we investigated the relationship between Glu504Lys polymorphism in the acetaldehyde dehydrogenase 2 (ALDH2) gene, a key enzyme of alcohol metabolism, and the risk of having T2DM in Chinese Han CAD patients. We enrolled 542 CAD patients (180 women and 362 men) and 309 CAD-/DM- subjects (152 women and 157 men). T2DM was confirmed in 47.4% of CAD patients. Logistic and linear regression analyses showed that ALDH2 mutant genotypes ((*)1/(*)2 and (*)2/(*)2) were an independent risk factor for both T2DM in female CAD patients, even after controlling for alcohol consumption (OR=1.95, P=0.043), and fasting plasma glucose (FPG) in CAD-/DM- women (P=0.015), whereas the association with FPG disappeared after controlling for high-sensitivity C-reactive protein, a classic inflammatory biomarker. However, there was no relationship between the ALDH2 genetic polymorphism and T2DM or FPG in men. These findings suggest that the ALDH2 polymorphism is associated with an increased risk of T2DM in female CAD patients, and this association could be causal on the basis of the association between the polymorphism and FPG, which is partly explained by an increased inflammatory status. These findings will benefit the screening and treatment of a high-risk population in East Asians.