Aldehyde Dehydrogenase 2 Rs671 Polymorphism Research Articles

Interactions between ALDH2 rs671 polymorphism and lifestyle behaviors on coronary artery disease risk in a Chinese Han population with dyslipidemia: A guide to targeted heart health management

BackgroundBoth aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism and lifestyle behaviors are involved in coronary artery disease (CAD), while the interaction between them is currently unknown.MethodsA nested case-control study was conducted in 161 patients with CAD and 495 controls in dyslipidemia population in Yinzhou District, Ningbo, Zhejiang Province, China, in August 2013. Anthropometric data and blood samples were collected, demographic characteristics and lifestyle behaviors information were obtained by a face-to-face interview, dietary intake was assessed by a food frequency questionnaire, and genomic DNA was genotyped.ResultsCarriers with increasing number of A alleles had an elevated CAD risk compared with G allele carriers (adjusted OR = 1.483, 95% CI = 1.114–1.974). Carriers of rs671 A/G and A/A genotypes had a higher CAD risk than carriers of G/G genotype (adjusted OR = 1.492, 95% CI = 1.036–2.148). Similarly, individuals with rs671 A/A genotype had a higher CAD risk than individuals with A/G and G/G genotypes (adjusted OR = 2.161, 95% CI = 1.139–4.101). We found a borderline additive interaction between regular fried food intake and A/A and A/G genotypes, and a significantly additive interaction between sedentary/light physical activity and A/A and A/G genotypes.ConclusionsIndividuals with A/A or A/G genotypes of rs671 have a higher CAD risk, if they lack physical activity and take fried food regularly, than individuals with G/G genotypes. These findings can help to provide a guide to targeted heart health management.

ALDH2 rs671 polymorphism is associated with athletic status and muscle phenotypes in the Japanese population

Mitochondrial aldehyde dehydrogenase‐2 (ALDH2) scavenges reactive aldehyde products, such as 4‐hydroxy‐2‐nonenal. Previous studies confirmed that the ALDH2 rs671 polymorphism is associated with hypertension and cancer, probably because of increased oxidative stress. Undesirable effects of ALDH2 rs671 might also be expected in skeletal muscles. The purpose of the present study was to investigate the association of ALDH2 re671 polymorphism with athletic status and muscle phenotypes in the Japanese population.In the present study, 1,464 athletes (672 sprint/Power athletes, 631 mixed athletes, and 161 endurance) and 1,341 non‐athletes (538 men and 803 women) were included in the analysis. Saliva samples were collected with the Oragene DNA self‐collection kit. The ALDH2 rs671 polymorphism was genotyped using a TaqMan SNP genotyping assay. The non‐athletes completed a questionnaire about exercise habits and were subjected to a battery of tests to assess their muscular functions (including grip strength and the 30‐second chair stand test)The ALDH2 genotype frequencies among athletes and non‐athletes were in Hardy‐Weinberg equilibrium. The frequencies of the ALDH2 genotypes GG, GA, and AA were 56%, 37%, and 7% in the athletes, and 54%, 37%, and 9% in the non‐athletes, respectively. There was a significant difference of genotype frequencies between the athletes and the non‐athletes (p=0.008). Among the non‐athletes, those with GG and GA genotypes showed higher fitness score of grip strength (p=0.001) and the 30‐second chair stand test (p=0.013) than those with the AA genotype after adjusting for age, sex, and exercise habits.Our study shows that ALDH2 rs671 polymorphism is associated with athletic status and muscle phenotypes in the Japanese population, suggesting that impaired ALDH2 activity might attenuate muscular function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Causal Role of Alcohol Use in Adolescent Externalizing and Internalizing Problems: A Mendelian Randomization Study.

The co-occurrence of alcohol use and externalizing/internalizing problems threatens adolescents' mental health. Research on whether alcohol use and these problems are causal and the direction of the potential causal relationships is needed to understand the mechanisms of the co-occurrence. A Mendelian randomization analysis was conducted in which the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol use phenotypes. In total, 1,608 Chinese adolescents (mean age 14.11±1.83years) were genotyped for the ALDH2 rs671 polymorphism. Three externalizing problems (aggression, delinquency, and attention problems) were measured with the Youth Self-Report inventory, and 2 internalizing problems (depression and anxiety) were measured with the self-reported Children's Depression Inventory and the Trait subscale of the State-Trait Anxiety Inventory. Alcohol use was positively associated with all 3 externalizing and 2 internalizing problems, and the ALDH2 polymorphism had a significant effect on alcohol use. Aggression and attention problems were also significantly affected by the ALDH2 polymorphism, whereas no significant association was observed between the ALDH2 polymorphism and delinquency, anxiety, or depression. The results suggest that alcohol use is a cause of adolescent aggression and attention problems but not adolescent delinquency, anxiety, or depression.

Associations between aldehyde dehydrogenase 2 (ALDH2) rs671 genetic polymorphisms, lifestyles and hypertension risk in Chinese Han people

Hypertension is a multiple factor disease which was influenced by gene, environment, and lifestyle. Several studies confirmed that the ALDH2 rs671 polymorphism is associated with hypertension. However, the evidence remains inconclusive. Whether lifestyle affects blood pressure in different genotype groups have not been clarified, either. The subjects were adult Chinese Han people who received health examination in the period from December 2014 to December 2015. Detection of the ALDH2 r671 polymorphism was determined by polymerase chain reaction. Lifestyle data were collected using self-administered questionnaires. Basic characteristics and fasting venous blood sample were collected at baseline. 4018 subjects were eligible for participation.The frequencies of the ALDH2 rs671 genotype were 68.67% (GG), 28.67%(GL), 2.66%(LL), respectively. Pepole who harbored the L allele were less likely to develop incident hypertension. There was a significant association between food frequency and hypertension in the L genotype group. Fried food intake was significantly increased the risk of hypertension in the L genotype group. Our study suggested that ALDH2 rs671 L-genotypes are protective factors for hypertension in Han Chinese. Consumption of fried food accelerated the development of hypertension in individuals with poor metabolism of acetaldehyde.

Effects of alcohol consumption, ALDH2 rs671 polymorphism, and Helicobacter pylori infection on the gastric cancer risk in a Korean population.

The effect of alcohol consumption on the risk of gastric cancer (GC) has not yet been fully elucidated, and an aldehyde dehydrogenase 2 (ALDH2) polymorphism, rs671, is a genetic variant that influences alcohol consumption in East Asians. Additionally, the discrepancy between the Helicobacter pylori (H. pylori) infection prevalence and GC incidence across Asian countries has not been explained. This study evaluated the effects of alcohol consumption and genetic susceptibility to defective acetaldehyde metabolism on the GC risk and their interactions with H. pylori infection. This study included 450 Korean GC cases and 1,050 controls recruited at the National Cancer Center. Data for 795 patients and 4,893 controls were used for further confirmation of the effect of rs671. Increased GC risks were evident for rs671 A allele carriers (odds ratio (OR), 1.23; 95% confidence interval (CI), 1.08-1.41) and H. pylori-infected individuals (OR, 7.07; 95% CI, 4.60-10.86), but no dose-response association with alcohol consumption was observed. Furthermore, the interactions between these factors were not significant. This study has demonstrated that alcohol consumption and rs671 should be considered simultaneously when assessing the GC risk. Additionally, alcohol-related factors were not found to interact with H. pylori infection, and further studies evaluating other environmental factors are required to explain the Asian enigma.

Abstract 800: ALDH2 rs671 polymorphism and alcohol consumption in the risk of gastric cancer: A Mendelian randomization study

Abstract Background: The effect of increased alcohol consumption on the risk for gastric cancer (GC) has not been fully elucidated, due to the presence of confounders and gender differences. In this study, aldehyde dehydrogenase 2 (ALDH2) rs671, the genetic polymorphism related to the elimination of acetaldehyde, was used as an instrumental variable (IV) for Mendelian randomization analysis to dissect the role of alcohol in GC risk. Methods: The study included Korean 450 GC cases and 1,050 controls recruited at the National Cancer Center. Data of 795 GC patients and 4,893 controls from the Korean Centers for Disease Control were used for further validation. The odds ratios (OR) for the ALDH2 genotype and its interaction with alcohol consumption were estimated using multivariate logistic regression. The two-stage control function method was performed using rs671 as the IV for alcohol consumption. Results: All AG carriers had an OR of 1.26 (95% confidence interval, 1.11-1.42) compared with GG carriers. In a quantitative analysis of alcohol intake, the conventional OR was 1.21(1.09-1.36) and the IV-OR was 0.90(0.63-1.28). Females had low alcohol consumption and did not show a significant risk for GC while males had a high risk for GC. Conclusions: Alcohol consumption is not associated with a risk for GC by itself, and ALDH2 polymorphism should be considered simultaneously when assessing the risk. Females did not display an evident risk for GC regarding alcohol, partly due to their lower level of alcohol consumption. However, further dissection of gender difference is necessary. Citation Format: Jeongseon Kim, Sarah Yang, Jeonghee Lee, Il Ju Choi, Young Woo Kim, Keun Won Ryu, Joohon Sung. ALDH2 rs671 polymorphism and alcohol consumption in the risk of gastric cancer: A Mendelian randomization study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 800.

Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence from 31 case-control studies.

BackgroundAldehyde dehydrogenase 2 (ALDH2), a critical enzyme for the detoxification of alcohol, is associated with many types of cancers. To verify the relationship of ALDH2 rs671 G>A polymorphism and esophageal cancer (EC), we performed a meta-analysis of a total of 31 published data including 8,510 patients and 16,197 controls.MethodsThe pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixed or random-effects model. Heterogeneity (PH), publication bias, and sensitivity analysis were also determined.ResultsAlthough a protective effort was found in the rs671 homozygote comparison (AA/GG: OR=0.69; 95% CI=0.48–0.98), the heterozygote comparison was apparently associated with the risk of EC, particularly in the Chinese population (AG/GG: OR=1.39; 95% CI=1.03–1.87). Alcohol consumption remarkably increased this risk, especially in the AG genotype. Drinking men with the AG genotype appeared to show a higher risk (AG/GG: OR=4.39; 95% CI=1.24–6.55) than drinking women.ConclusionThe present meta-analysis provided advanced information regarding the association of the ALDH2 A>G polymorphism and EC. Taken together, insights from this study suggested an enhanced effect on the development of EC through a genetic–environmental interaction.

Meta-analysis of association between ALDH2 rs671 polymorphism and essential hypertension in Asian populations.

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) is an enzyme that oxidizes acetaldehyde into acetic acid during alcohol metabolism. Many studies indicate that the rs671 GG genotype in the ALDH2 gene may play a critical role in increasing the risk of essential hypertension (EH) associated with alcohol consumption, which predominantly occurs in men. However, the literature is inconclusive in this regard. This meta-analysis aims to derive a more precise estimation of the relationship between the rs671 polymorphism and EH for both male and female drinkers and nondrinkers. Ten cohort and case-control studies were included in the analysis with a total of 12,161 subjects; 7,062 patients and 5,099 healthy controls. Our results show that the rs671 GG genotype was associated with an increased risk of EH compared with the AG+AA genotype (OR = 1.27, 95 % CI = 1.17-1.37, p < 0.00001). When comparing male and female subjects, only among male individuals was a higher risk of EH found in the GG genotype compared with the AG+ AA genotype (OR = 1.59, 95 % CI = 1.40-1.80, p < 0.00001). By contrast, among female subjects, the risk of EH in the rs671 GG genotype did not differ from that detected in the AA + GG genotype. The proportion of patients with EH was significantly higher for the GG genotype carriers than for the AG+AA genotype carriers, both in the subset of drinkers (OR = 1.51, 95 % CI = 1.23-1.86, p < 0.0001) and in that of nondrinkers (OR = 1.22, 95 % CI = 1.01-1.47, p = 0.03). In addition, among carriers of the GG genotype, the risk of EH among the drinkers was similar to that found in the nondrinkers' subset (OR = 1.12, 95 %CI = 0.89-1.41, p = 0.34). Our meta-analysis demonstrates that the rs671 GG genotype increases the risks of EH, especially in men, and is independent of alcohol consumption.

The ALDH2 rs671 polymorphism affects post-stroke epilepsy susceptibility and plasma 4-HNE levels.

Recent studies have demonstrated the protective effect of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases. Increased levels of the potential ALDH2 substrate 4-hydroxynonenal (4-HNE) are involved in myocardial/cerebral ischemia accompanied by a high level of oxidative stress. In this investigation, we first performed a case-control study to explore the potential association of ALDH2 rs671 polymorphism and post-stroke epilepsy (PSE). Then, we performed an in vitro study to determine whether the overexpression of ALDH2 could decrease the level of oxidative stress and the apoptosis ratio induced by 4-HNE. There was a significant difference in the distribution of the allele and genotype frequencies of the rs671 polymorphism between PSE patients and ischemic stroke (IS) patients. Individuals with the rs671 A allele showed significantly higher levels of plasma 4-HNE. The overexpression of ALDH2 partially blocked the increased levels of malondialdehyde (MDA), reactive oxygen species (ROS) and apoptosis ratio induced by 4-HNE and also partially restored the ALDH2 activity in PC12 cells; these effects were reversed in the presence of εV1-2. Our results suggest that the ALDH2 rs671 polymorphism is associated with PSE susceptibility and affects the 4-HNE levels. Targeting ALDH2 might be a useful strategy for the treatment or prevention of PSE.

ALDH2rs671 Polymorphism and Coronary Heart Disease Risk Among Asian Populations: A Meta-Analysis and Meta-Regression

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) is the principal enzyme involved in alcohol metabolism in humans. Emerging evidence has shown that the common rs671 G>A (Glu504Lys) polymorphism in the ALDH2 gene might play a critical role in increasing the susceptibility to coronary heart disease (CHD), including myocardial infarction (MI); however, individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the relationship between the ALDH2 rs671 polymorphism and its influence on the susceptibility to CHD and MI. Nine case-control studies were included with a total of 7358 subjects, including 1961 CHD patients, 1040 MI patients, and 4357 healthy controls. Our meta-analysis results showed that the A variant of the ALDH2 rs671 polymorphism may be associated with increase risks of CHD (odds ratios [OR]=1.36, 95% confidence interval [CI]=1.06-1.75, p=0.017) and MI (OR=1.64, 95% CI=1.22-2.20, p=0.001). Univariate and multivariate meta-regression analyses showed no potential factors explained heterogeneity. No publication bias was detected in this meta-analysis. In conclusion, the current meta-analysis indicates that the A variant of the ALDH2 rs671 polymorphism may increase the risk of both CHD and MI among Asian populations.

A genome-wide association and gene–environment interaction study for serum triglycerides levels in a healthy Chinese male population

Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.