ALDH2 gene G487A polymorphism and coronary artery disease:
a meta-analysis including 5644 participants
* , Hui Wang
, Jing-jing Wu
, Hyun Jun Kim
, Xin-xing Yang
, Hong-yu Geng
Department of Geriatrics, First Afﬁliated Hospital of Nanjing Medical University, Nanjing, China
Institute of Clinical Medicine, First Afﬁliated Hospital of Nanjing Medical University, Nanjing, China
Department of cardiology, First Afﬁliated Hospital of Nanjing Medical University, Nanjing, China
Department of Nephrology, First Afﬁliated Hospital of Nanjing Medical University, Nanjing, China
Department of Physiology, University of Cincinnati, Cincinnati, USA
Department of Geriatrics, Nanjing General Hospital, Nanjing, China
Received: February 27, 2017; Accepted: September 20, 2017
Several studies indicate the mitochondrial Aldehyde Dehydrogenase-2 (ALDH2) gene G487A polymorphism may be correlated with coronary
artery disease (CAD) susceptibility, but a clear consensus has yet to be reached. To elucidate the relationship between the ALDH2 gene G487A
polymorphism and CAD within the Chinese population, a meta-analysis of 5644 subjects from nine individual studies was performed. Pooled
odds ratios (ORs) and their corresponding 95% conﬁdence intervals were assessed using random or ﬁxed-effect models depending the hetero-
geneity existence or not. Our meta-analysis found a signiﬁcant association between ALDH2 gene G487A polymorphism and CAD in the Chinese
population under allele (OR: 1.830, 95% CI: 1.560–2.140, P = 1.36 9 10
), recessive (OR: 1.920, 95% CI: 1.530–2.390, P = 1.20 9 10
dominant (OR: 1.593, 95% CI: 1.336–1.900, P = 2.22 9 10
), homozygous (OR: 2.280, 95% CI: 1.810–2.870, P = 3.17 9 10
heterozygous genetic models (OR: 3.330, 95% CI: 2.070–5.370, P = 7.81 9 10
). The positive correlation between the ALDH2 gene G487A
polymorphism and CAD makes the mutation a strong candidate as a genetic risk marker for CAD. Through further analysis, we also found that
A allele carriers of ALDH2 gene G487A polymorphism may be particularly susceptible to CAD.
coronary artery disease
Coronary artery disease (CAD) is a disease that affects many middle-
aged and elderly people and is usually accompanied by hypertension,
diabetes mellitus and dyslipidaemia. ALDH2 is a mitochondria enzyme
distributed in the various tissues. CAD describes a group of cardio-
vascular diseases that collectively cause more deaths than any other
disease globally. The conﬂuence of genomic and environmental risk
factors make CAD difﬁcult to treat effectively, but research on the
genomic basis of CAD, has tremendously deepened our understand-
ing of this complex disease.
Mitochondrial aldehyde dehydrogenase-2 (ALDH2) is an enzyme
known primarily for its role in alcohol metabolism. Once ethanol is
converted to acetaldehyde, ALDH2 facilitates its conversion to
acetate. More interestingly, ALDH2 was also found to play signiﬁcant
role in cardiac protection in a range of settings. It was found to allevi-
ate cardiac ischaemic injury by removing 4-HNE, a highly reactive
compound associated with oxidative stress  and contributes GTN
biotransformation by converting it to 1, 2-glycerin dinitrate .
ALDH2 was also able to reverse the cardiac hypertrophy caused by
chronic alcohol consumption and improve the systolic dysfunction of
alcoholic cardiomyopathy .
Human ALDH2, located on 12q24, contains 13 exons. The G487A
polymorphism causes the glutamate at position 504 to be replaced by
a lysine residue on exon 12 (rs671). While the mutation frequency of
this polymorphism is only 5% in Western populations, East Asian
populations can have mutations frequencies ranging from 30% to
50% . The G487A mutation is associated with a signiﬁcant
decrease in enzymatic activity and reduced biological function
.Regression analysis showed that the ALDH2 gene G487A poly-
morphism was associated with decreased high-density lipoprotein
Yan-yan Li and Hui Wang contribute equally to this work.
*Correspondence to: Yan-yan LI
ª 2017 The Authors.
Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited.
J. Cell. Mol. Med. Vol 22, No 3, 2018 pp. 1666-1674