Genetic polymorphisms in the <i>ALDH2</i> gene and the risk of ischemic stroke in a Chinese han population

Sun, Shida; He, Jun; Zhang, Yao; Xiao, Rongjun; Yan, Mengdan; Ren, Yulin; Zhu, Yaobin; Jin, Tianbo; Xia, Ying

doi:10.18632/oncotarget.21803

Cited by 10 publications

(9 citation statements)

References 25 publications

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“…A meta-analysis of 83 prospective studies with 5,99,912 current alcoholic beverage drinkers mainly of European descent suggested that stroke incidence increased steadily with the alcohol intake [ 11 ]. This aligns with epidemiologic and genetic studies in China where U-shaped associations were found between self-reported alcohol intake and the incidence of ischemic stroke, intracerebral hemorrhage, and total stroke [ 12 , 13 ]. Moderate alcohol intake (100 g per week) was associated with a lower risk of stroke [ 13 ].…”

Section: Introductionsupporting

confidence: 84%

Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

Lin

Nfor

et al. 2021

J Transl Med

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Background Alcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10–20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption. Methods Data were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean ± SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p < 0.0001). ALDH2 rs671 was not associated with either hemorrhagic or ischemic stroke among alcohol drinkers. However, the risk of developing hemorrhagic stroke was significantly higher among ADH1B rs1229984 TC + CC individuals who drank alcohol (odds ratio (OR), 4.85; 95% confidence interval (CI) 1.92–12.21). We found that the test for interaction was significant for alcohol exposure and rs1229984 genotypes (p for interaction = 0.016). Stratification by alcohol exposure and ADH1B rs1229984 genotypes showed that the risk of developing hemorrhagic stroke remained significantly higher among alcohol drinkers with TC + CC genotype relative to those with the TT genotype (OR, 4.43, 95% CI 1.19–16.52). Conclusions Our study suggests that the ADH1B rs1229984 TC + CC genotype and alcohol exposure of at least 150 ml/week may increase the risk of developing hemorrhagic stroke among Taiwanese adults.

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Section: Introductionsupporting

confidence: 84%

Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

Lin

Nfor

et al. 2021

J Transl Med

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“…In contrast, Xu et al found that the prevalence of the G-allele of ALDH2 in the rs671 G>A polymorphism was higher in controls than in patients with IS, and stated that the A-allele and the GA genotype exerted protective effects against IS (A vs G, OR=0.37, 95% CI=0.19–0.72; GA vs GG, OR=0.30, 95% CI=0.14–0.65) 22. Other studies, such as those by Qu et al29 and Sun et al,28 did not find any significant relationship between the ALDH2 rs671 G>A polymorphism and IS risk.…”

Section: Discussionmentioning

confidence: 77%

<p>Aldehyde dehydrogenase 2 rs671G>A polymorphism and ischemic stroke risk in Chinese population: a meta-analysis</p>

Xu¹,

Hu²,

Li³

et al. 2019

NDT

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Introduction: Recently, molecular epidemiological studies have suggested that aldehyde dehydrogenase 2 (ALDH2) rs671 G>A polymorphism may be a risk factor for ischemic stroke (IS). However, the results reported have not been consistent. Methods: We conducted the meta-analysis to explore the precise association between ALDH2 rs671 G>A polymorphism and IS risk. Five online databases were searched and the relative studies were reviewed from inception to October 1, 2018. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated in each genetic model of the general and subgroup. Furthermore, the heterogeneity, accumulative analyses, sensitivity analyses and publication bias were calculated simultaneously. Results: Overall, nine case-control studies involving 6,129 subjects were included in this meta-analysis. All studies were focused on the Chinese population and some significant associations were found between ALDH2 rs671 G>A polymorphism and IS risk (A vs G: OR=1.29, 95% CI=1.01–1.65, P =0.04, I 2 =78.2%; AA vs GG: OR=1.86, 95% CI=1.27–2.21, P <0.01, I 2 =11.3%; AA vs GG + GA: OR=1.67, 95% CI=1.27–2.19, P <0.01, I 2 =0%). Some significant and similar results were also observed in the subgroup analysis. Conclusion: Our meta-analysis indicates that the ALDH2 rs671 G>A polymorphism may play an important role in the occurrence of IS by reducing the activity of ALDH2 and interfering with the metabolic processes involving acetaldehyde.

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“…Combining two data sources, we demonstrated the relationship between stroke and the rs12514417 polymorphism and its impact on alcohol consumption. Our main finding suggests that the ALDH7A1 rs12514417 TG + GG genotype may be associated with a 1.6-fold increased risk of ischemic stroke in subjects who drink more than 150 ml of alcohol per week[ 6 , 7 , 22 – 24 ]. This is the first study to identify the relationship between ALDH7A1 mutation and ischemic stroke, suggesting a change in lifestyle, specifically a reduction in alcohol consumption could reduce disease risk in carriers of this variant.…”

Section: Discussionmentioning

confidence: 99%

ALDH7A1 rs12514417 polymorphism may increase ischemic stroke risk in alcohol-exposed individuals

Lin

Nfor

et al. 2022

Nutr Metab (Lond)

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Background: Epidemiological studies have identified common risk factors for cerebral stroke worldwide. Some of these factors include hypertension, diabetes, smoking, excessive drinking, and dyslipidemia. It is important to note, however, that genetic factors can also contribute to the occurrence of stroke. Here, we evaluated the association of ischemic stroke with rs12514417 polymorphism of the alcohol metabolizing gene, aldehyde dehydrogenase 7A1 (ALDH7A1) and alcohol consumption. Methods: Taiwan Biobank (TWB) data collected between 2008 and 2015 were available for 17,985 subjects. The odd ratios for stroke were obtained using logistic regression models. Results: Among eligible subjects (n = 17,829), 897 had ischemic stroke and 70 had hemorrhagic stroke. Subjects with ischemic stroke were older (mean ± SE, 58.45 ± 8.19 years vs. 48.33 ± 10.89 years, p < 0.0001) and had a higher body mass index (BMI) than the stroke-free individuals. The risk of ischemic stroke was significantly higher among subjects with the ALDH7A1 rs12514417 TG + GG genotype who also consumed alcohol at least 150 ml/week (odds ratio (OR), 1.79; 95% confidence interval (CI), 1.18–2.72). We found that rs12514417 genotype and alcohol consumption (at least 150 ml/week) showed a significant interaction (p for interaction = 0.0266). Stratification based on alcohol exposure and ALDH7A1 rs12514417 genotypes indicated that ischemic stroke risk was significantly higher among alcohol drinkers with the TG + GG genotype than in those with the TT genotype (OR, 1.64, 95% CI: 1.15–2.33). Conclusion: Our study suggests that the combination of ALDH7A1 rs12514417 TG + GG genotype and alcohol exposure of at least 150 ml/week may increase the risk of ischemic stroke in Taiwanese adults.

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Genetic polymorphisms in the ALDH2 gene and the risk of ischemic stroke in a Chinese han population

Cited by 10 publications

References 25 publications

Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

<p>Aldehyde dehydrogenase 2 rs671G>A polymorphism and ischemic stroke risk in Chinese population: a meta-analysis</p>

ALDH7A1 rs12514417 polymorphism may increase ischemic stroke risk in alcohol-exposed individuals

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Genetic polymorphisms in the ALDH2 gene and the risk of ischemic stroke in a Chinese han population

Cited by 10 publications

References 25 publications

Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke

<p>Aldehyde dehydrogenase 2 rs671G&gt;A polymorphism and ischemic stroke risk in Chinese population: a meta-analysis</p>

ALDH7A1 rs12514417 polymorphism may increase ischemic stroke risk in alcohol-exposed individuals

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<p>Aldehyde dehydrogenase 2 rs671G>A polymorphism and ischemic stroke risk in Chinese population: a meta-analysis</p>