Dataset Information

Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism is associated with hypertension risk in Asians: a meta-analysis.

ABSTRACT:

Background

The association of the aldehyde dehydrogenases-2 (ALDH2) Glu504Lys polymorphism and hypertension in Asians has been investigated. This meta-analysis aims to comprehensively assess the influence of this polymorphism on the hypertension risk.

Method

An electronic literature search was conducted using the following database: PubMed, Embase and China National Knowledge Infrastructure (CNKI) till to Mar 25th, 2015. The strength of the association between statins and fractures risk was calculated with the OR and respective 95% CIs. The random effect model was used.

Results

Nine studies evaluating the relationship between ALDH2 Glu504Lys polymorphism and hypertension risk in Asians were selected in this meta-analysis. A total of 12161 subjects were included. The data showed that ALDH2 Glu504Lys polymorphism could increase the risk of hypertension of Asians (OR = 1.31; 95% CI, 1.18-1.47; P < 0.00001). In the subgroup analysis of race, both Japanese and Chinese with ALDH2 Glu504Lys polymorphism showed increased hypertension risk (OR = 1.23; 95% CI, 1.09-1.38; P = 0.0006 and OR = 1.46; 95% CI, 1.21-1.77; P = 0.0001), respectively. In the subgroup analysis of gender, males with this polymorphism showed increased hypertension risk (OR = 1.59; 95% CI, 1.40-1.80; P < 0.00001). However, females did not showed this result (OR = 0.94; 95% CI, 0.69-1.30; P = 0.71). When considered alcohol consumption, we found that drinkers and non-drinkers all had increased hypertension risk, if they carried this polymorphism.

Conclusion

This meta-analysis suggested that ALDH2 Glu504Lys polymorphism was a risk factor of hypertension in Asians.

SUBMITTER: Jia K

PROVIDER: S-EPMC4565253 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism is associated with hypertension risk in Asians: a meta-analysis.

Jia Kui K Wang Honglei H Dong Pingshuan P

International journal of clinical and experimental medicine 20150715 7

<h4>Background</h4>The association of the aldehyde dehydrogenases-2 (ALDH2) Glu504Lys polymorphism and hypertension in Asians has been investigated. This meta-analysis aims to comprehensively assess the influence of this polymorphism on the hypertension risk.<h4>Method</h4>An electronic literature search was conducted using the following database: PubMed, Embase and China National Knowledge Infrastructure (CNKI) till to Mar 25th, 2015. The strength of the association between statins and fracture ...[more]

PMID: 26379870

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Project description:Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671; 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p < 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p < 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all Pinteraction: <0.05). Binge drinking superimposed on regular alcohol use exclusively further worsened LA booster pump function compared to regular drinking without binge use (1.66 ± 0.57 vs. 1.97 ± 0.56 1/s, p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06-2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.

Project description:BackgroundAldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined.MethodsWe examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 -/- mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 -/- mice.ResultsIn humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 -/- and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 -/- mice. Aldh2 -/- tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 -/- mice than in WT mice.ConclusionsALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a "premature lung aging" effect.

Dataset Information

Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism is associated with hypertension risk in Asians: a meta-analysis.

Background

Method

Results

Conclusion

Publications

Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism is associated with hypertension risk in Asians: a meta-analysis.

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