Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary syndrome

Abstract

This study aimed to investigate the association of the aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism, which exists in 30–50% of East Asians, and risk of acute coronary syndrome (ACS). We enrolled 1092 unrelated Han Chinese, including 546 with ACS and 546 age- and sex-matched controls. Subjects with ALDH2 mutant genotypes showed significantly higher ACS than did controls (46.7% versus 31.9%, P < 0.001). Logistic regression analysis revealed the ALDH2 mutant independently associated with ACS (odds ratio [OR] 1.95, 95% confidence interval [CI]: 1.31–2.92, P = 0.001), but the association was weaker on adjusting for alcohol consumption (OR 1.82, 95% CI: 1.23–2.70, P = 0.003). Similar results were found in a subgroup analysis of patients with primary ST-segment elevation myocardial infarction (STEMI). The ALDH2 mutant was significantly associated with level of high-sensitivity C-reactive protein (hs-CRP) in patients with ACS (P = 0.002) and in controls (P = 0.009) and number of circulating endothelial progenitor cells (EPCs) (P = 0.032); furthermore, inclusion of hs-CRP level and EPCs number as independent variables in regression analysis reduced the importance of ALDH2 polymorphism in ACS or primary STEMI. However, ALDH2 polymorphism was not associated with number of coronary arteries with significant stenosis, Gensini score or flow-mediated dilation of the brachial artery. Our results suggest that ALDH2 mutation is a genetic risk marker for ACS, which is explained in part by alcohol consumption, inflammation and number of circulating EPCs.

The Glu504Lys Polymorphism of Aldehyde Dehydrogenase 2 Contributes to Development of Coronary Artery Disease

“…Our group found that carriers of the ALDH2 *504Lys allele drink significantly less than carriers of the wild-type ALDH2 (Xu et al 2011), which was consistent with other studies in Chinese populations (Muramatsu et al 1995;Ding et al 2008). Additionally, when alcohol consumption was incorporated into the regression analysis model as an independent variable, the correlation between ALDH2 *504Lys allele and ACS decreased but was still significant (Xu et al 2011).…”

“…Additionally, when alcohol consumption was incorporated into the regression analysis model as an independent variable, the correlation between ALDH2 *504Lys allele and ACS decreased but was still significant (Xu et al 2011). Studies conducted by Japanese and South Korean scholars reached similar conclusions (Takagi et al 2002;Jo et al 2007).…”

“…Based on these seemingly contradictory results, we conducted a case-control study with a larger sample size (1,092 cases) to explore the relationship between ALDH2 polymorphism and acute coronary syndrome (ACS) in Han Chinese (Xu et al 2011). The results revealed that the ALDH2 *504Lys allele is an independent genetic risk factor for ACS in Han Chinese.…”

“…In 2012, a genome-wide association (GWA) study further confirmed that the ALDH2 Glu504Lys polymorphism is associated with the susceptibility to CAD (Takeuchi et al 2012). Many groups, includ-ing ours, recently explored underlying mechanisms for the effects of this polymorphism on CAD (Churchill et al 2009;Guo et al 2010;Xu et al 2011;Xue et al 2012;. Several studies, including GWA studies, found that this polymorphism is also related to well-known cardiovascular risk factors, such as dyslipidemia (Hao et al 2010;Wei et al 2013), hypertension (Kato et al 2011), diabetes (Wang et al 2011), or hyperglycemia .…”

Emerging Associations of the ALDH2*2 Polymorphism with Disease Susceptibility

“…Acute coronary syndrome includes physiological conditions such as elevated blood pressure, heart attacks, and hypertension. Several studies have shown that the ALDH2*2 mutation is an independent risk factor for ACS [63][64][65][66]. More specifically, other studies have confirmed that an ALDH2 mutation is a strong risk factor for symptoms of elevated blood pressure and hypertension in males who consume high amounts of alcohol [67,68].…”