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

Abstract

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 CADÀ/DMÀ 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 (OR¼1.95, P¼0.043), and fasting plasma glucose (FPG) in CADÀ/DMÀ women (P¼0.015), 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.

Aldehyde dehydrogenase 2 (ALDH2) polymorphism gene and coronary artery disease risk: a meta-analysis

“…The characteristics of each case-control are listed in Table 1. There were 5 cases-controls of MI (Takagi et al, 2002;Xue, 2007;Jo et al, 2007;Li, 2008;Bian et al, 2010), 4 of CHD (Xu et al 2007;Guo et al, 2010;Yuguo, 2010;Ping, 2012), 2 of CHD plus diabetes mellitus (Chao, 2009;Xu et al, 2010), and 1 of acute coronary syndrome (Xu et al, 2011). Four studies included unpublished material (Chao, 2009;Yuan, 2009;Yijie, 2010;Ping, 2012).…”

“…After reading the titles and abstracts, 65 studies were excluded because they did not exmaine CAD risk and the ALDH2 gene. The full-texts of the remaining 17 articles were reviewed (Takagi et al, 2002;Xue et al, 2007;Jo et al, 2007;Li, 2008;Wada et al, 2008;Chao, 2009;Yuan, 2009Yuan, , 2010Guo et al, 2010;Hao et al, 2010;Yijie, 2010;Yuguo, 2010;Xu et al, 2007Xu et al, , 2010Xu et al, , 2011Kotani et al, 2012;Ping, 2012). Next, an additional 6 articles were excluded [2 were repeated or overlapping studies (Li, 2008;Yuan, 2009), 2 were not case-control studies (Ji, 2008;Li, 2012); and 2 did not include the full-text (Wada et al, 2008;Kotani et al, 2012)].…”

Induced pluripotent stem cells: at the heart of cardiovascular precision medicine

“…91 This polymorphism also has been linked to increased risk of CAD 109 and complications from diabetes. 110 Ebert et al first used hiPSC-CMs derived from a cohort of sex-matched East Asian individuals carrying this polymorphism and showed that these cells experienced more oxidative stress and apoptosis secondary to toxic aldehyde buildup during ischemic injury. 91 These effects were mediated by reactive oxygen species (ROS)-mediated upregulation of JNK, such that administration of JNK inhibitor (JIP) restored ROS level as well as viability post-ischemia.…”

Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system

“…The single-nucleotide polymorphism that generates a Glu-to-Lys change at position 487 (E487K) of the cardioprotective enzyme aldehyde dehydrogenase 2 (ALDH2*2) (1, 2) has been linked to both an increased risk of CAD and more severe outcomes (3-6), a higher incidence of hypertension and cancer, and an increase in complications from type 2 diabetes (7-9). The ALDH2*2 genotype is present in ~8% of the human population, predominantly in people of East Asian heritage.…”