Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for esophageal cancer in a Chinese population

Ding, Jiannan; Li, Suping; Cao, Hongyan; Wu, Jianzhong; Gao, Chang–Ming; Liu, Yanting; Zhou, Jian; Chang, Joon-Hyuk; Yao, G.

doi:10.1038/jhg.2009.129

Cited by 33 publications

(36 citation statements)

References 13 publications

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“…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).…”

Section: Underlying Mechanisms Of * 504lys Allele Influencing Cadsupporting

confidence: 78%

“…Previous studies on ALDH2 polymorphism and disease have usually focused on the relationship between ALDH2 and alcohol-related diseases, such as hepatitis, cirrhosis, alcoholic cardiomyopathy, and digestive system tumors (Yokoyama et al 1996;Tanabe et al 1999;Ding et al 2008;Ma et al 2009). In addition to these disease, the Glu504Lys polymorphism is also shown to be associated with stroke, neurodegenerative disorders like Parkinson's disease and Alzheimer's disease, fanconi anemia, radiodermatitis, osteoporosis, the process of aging, pain and so on (Chen et al 2014).…”

Section: Aldh2 Polymorphism and Cadmentioning

confidence: 99%

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

Sun

Shang

et al. 2014

Tohoku J. Exp. Med.

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Coronary artery disease (CAD) is a leading cause of death, and its genetic mechanism has been always a major research concern. Recently, increasing evidence has indicated that the aldehyde dehydrogenase 2 (ALDH2) polymorphism, known as Glu504Lys (rs671), may contribute to CAD development. ALDH2 has been well known as a key enzyme in alcohol metabolism, and subjects with *504Lys allele exist in 30-50% of the East Asian population (6% of the world's population). However, recent studies have indicated that the *504Lys allele of the ALDH2 gene may be associated with the pathogenesis of CAD in a given number of Chinese, Japanese, and Korean people. This discovery has been further confirmed by a genome-wide association study in 2012 that identified the link of ALDH2 Glu504Lys polymorphism to CAD susceptibility. ALDH2 may therefore serve as an important target for CAD intervention. Several studies have suggested that ALDH2 polymorphism plays an important role in the progress of CAD through multiple mechanisms, including the regulation of alcohol consumption, inflammation, endothelial progenitor cells, oxidative stress, asymmetric dimethylarginine, endothelial nitric oxide synthase, and other CAD-promoting factors. Furthermore, the ALDH2 Glu504Lys polymorphism has been shown to be associated with certain traditional cardiovascular risk factors, such as dyslipidemia, hypertension, and diabetes mellitus or hyperglycemia. In this review, we update the current research on the association of the Glu504Lys polymorphism with the susceptibility to CAD. We also highlight and discuss the underlying mechanisms, by which the ALDH2 Glu504Lys polymorphism may be targeted for the prevention and treatment of CAD.

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Section: Underlying Mechanisms Of * 504lys Allele Influencing Cadsupporting

confidence: 78%

Section: Aldh2 Polymorphism and Cadmentioning

confidence: 99%

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

Sun

Shang

et al. 2014

Tohoku J. Exp. Med.

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“…These results are consistent with other studies on the Chinese. 37,38 In this study, we also found that there was a higher prevalence of ALDH2 mutant genotypes in DM patients than in non-DM patients; binary logistic regression analysis showed that ALDH2 mutant genotypes were independent risk factors of T2DM in CAD patients.…”

Section: Discussionmentioning

confidence: 49%

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

Chen

et al. 2009

Hypertens Res

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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.

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“…We also found that it was not ADH2 but ALDH2 polymorphisms that had a significant interaction with heavy alcohol consumption in the development of hepatocellular carcinoma (HCC) [9] . In the present study, both ADH2 G allele and ALDH2 A allele significantly increased the risk of esophageal cancer development.…”

Section: Discussionmentioning

confidence: 80%

Polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 and esophageal cancer risk in Southeast Chinese males

Ding¹,

Li²,

Cao³

et al. 2009

WJG

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AIM:To evaluate the impact of alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms on esophageal cancer susceptibility in Southeast Chinese males. METHODS:Two hundred and twenty-one esophageal cancer patients and 191 healthy controls from Taixing city in Jiangsu Province were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase chain reaction and denaturing highperformance liquid chromatography. Unconditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence interval (CI). RESULTS:The ADH G allele carriers were more susceptible to esophageal cancer, but no association was found between ADH2 genotypes and risk of esophageal cancer when disregarding alcohol drinking status. Regardless of ADH2 genotype, ALDH2G/A or A/A carriers had significantly increased risk of developing esophageal cancer, with homozygous individuals showing higher esophageal cancer risk than those who were heterozygous. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk; the OR was 3.05 (95% CI: 1.49-6.25). Compared with non-drinkers carrying both ALDH2 G/G and ADH2 A/A, drinkers carrying both ALDH2 A allele and ADH2 G allele showed a significantly higher risk of developing esophageal cancer (OR = 8.36, 95% CI: 2.98-23.46). CONCLUSION:Both ADH2 G allele and ALDH2 A allele significantly increase the risk of esophageal cancer development in Southeast Chinese males. ALDH2 A allele significantly increases the risk of esophageal cancer development especially in alcohol drinkers. Alcohol drinkers carrying both ADH2 G allele and ALDH2 A allele have a higher risk of developing esophageal cancer.

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Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for esophageal cancer in a Chinese population

Cited by 33 publications

References 13 publications

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

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

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

Polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 and esophageal cancer risk in Southeast Chinese males

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