ALDH2 genotype‐associated differences in the acute effects of alcohol on P300, psychomotor performance, and subjective response in healthy young Korean men: a double‐blind placebo‐controlled crossover study

Shin, Hee‐Young; Shin, Il‐Seon; Yoon, Jin‐Sang

doi:10.1002/hup.755

Cited by 8 publications

(14 citation statements)

References 31 publications

(33 reference statements)

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“…A previous study on Health Risk Appraisal Models, which made use of information on ALDH2 variants to evaluate disease outcomes, supported this notion, showing high detection rate 67. In line with this, the inclusion of genetic information is now regarded as a very useful tool for educating alcohol intake and drinking behavior properly in community and/or clinical settings,68 yet still, such a genetic education model is not available in Korea.…”

Section: A Genetic Education Model For Alcohol Consumption and Relatementioning

confidence: 86%

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea

2017

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Alcohol consumption is a serious health issue in Korea in terms of the amount consumed and the behavior related to its consumption. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism that degrades acetaldehyde to nontoxic acetic acid. The enzyme is coded by the ALDH2 gene, which is commonly polymorphic in East Asian populations. A point mutation in the ALDH2 gene (the rs671 allele) yields an inactive form of ALDH2 that causes acetaldehyde accumulation in the body after alcohol consumption, thereby inhibiting normal alcohol metabolism. Individuals who are homozygous for polymorphism in ALDH2 tend to refrain from drinking alcohol, decreasing their chances of developing alcoholism and exposure to the associated risks. Mendelian randomization (MR) studies have demonstrated that alcohol consumption predicted by ALDH2 genotype is causally related to cardiovascular risks. Moreover, recent MR studies suggest that the ALDH2 variant has mechanistic effects on some disease outcomes or mortality through increased blood levels of acetaldehyde, showing differences therein between heterozygotes (ALDH2*2*2) and homozygotes (ALDH2*1*2) in those who consume alcohol. Accordingly, consideration of ALDH2 genotype in alcohol prevention programs is warranted. In conclusion, strategies that incorporate genetic information and provide an evidential basis from which to help people make informed decisions on alcohol consumption are urgently required.

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Section: A Genetic Education Model For Alcohol Consumption and Relatementioning

confidence: 86%

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea

2017

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“…All subjects consumed the test or placebo beverages in random sequence over the three time points (with an interval of a week for three consecutive weeks). Each beverage was made to a volume of 500 ml and consumed over 10 min at room temperature from an opaque bottle, through a stopper packed with spirit soaked cotton wool, to provide olfactory masking (Shin et al, 2006). The timetable for each evaluation session is shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults

Chen

et al. 2012

J. Zhejiang Univ. Sci. B

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Event-related potential (ERP) is a reliable neuroelectric measure of brain activity that helps to confirm the assessment of mental status and cognitive impairment. Many studies have reported that alcoholics show a significantly lower ERP P300 amplitude than the norm. In the present study, ERP P300 waves were measured to evaluate the effect of citric acid on cognitive function during excessive alcohol consumption in healthy adults. Five volunteers were selected through clinical interview, physical examination, and psychiatric assessment for participation in this study. In a double-blind placebo-controlled before-after design, each subject was treated with 5 ml/kg body weight alcohol, 5 ml/kg body weight alcohol and 1 mg citric acid, or a placebo on three separate occasions, one week apart. ERP P300, blood biochemical indicators, blood alcohol concentrations (BACs) and acetaldehyde concentrations were assessed. Repeated measure analysis of variance (ANOVA) with a within-subjects factor was used to evaluate differences in blood biochemical indicators, BACs, blood acetaldehyde concentrations, and ERP P300 in the three sessions of assessments. Several blood biochemical indicators showed significant differences between treatments, including the levels of cholinesterase (CHE), total bile acid (TBA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and glycylproline dipeptidyl aminopeptidase (GPDA). BACs after consumption of alcohol alone or citric acid with alcohol were significantly higher compared to those after placebo treatment (P<0.05). There were no significant differences in blood acetaldehyde concentrations between the treatments. The P300 amplitudes on the frontal (Fz), central (Cz), and parietal (Pz) regions of the scalp after consumption of alcohol were significantly lower than those after consumption of the placebo or citric acid with alcohol (P<0.05), while there were no significant differences between the latter two treatments. The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption. It may also affect some blood biochemical indicators, but the specific mechanisms need further research.

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“…The ethnicity difference is important for studying the risk of developing OUD and the treatment outcomes [55,56]. Unfortunately, other studies focused only on the effects of ALDH2 gene polymorphisms in modulating alcohol-related cognitive function [19,20] and ignored the changes caused by other classes of substance abuse. Kim et al [19] found that the psychomotor performance of patients with ALDH2*1/*2 was significantly poorer than that of those with the ALDH2*1/*1 genotype after alcohol consumption.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, ALDH2 polymorphisms are associated with the effects of alcohol on various neurophysiological and psychomotor functions [19,20]. All these studies [17][18][19][20] hypothesized that the ALDH2 gene polymorphisms affect aldehyde metabolism and cognitive function. We therefore hypothesize that the ALDH2 gene affects the cognitive functions in patients with OUD as it does in alcohol abusers, and that it leads to the underlying cognitive deficits in OUD.…”

Section: Introductionmentioning

confidence: 99%

ALDH2 Gene: Its Effects on the Neuropsychological Functions in Patients with Opioid Use Disorder Undergoing Methadone Maintenance Treatment

Lee

Wang

Chang

et al. 2020

Clin Psychopharmacol Neurosci

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Objective: Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2 (ALDH2) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT). Methods: OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors' Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R. Results: We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2＋*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p = 0.03), significantly lower hit reaction time T-scores (p = 0.04), and significantly lower WMS-R visual memory index scores (p = 0.03) than did patients with the ALDH2 1*/*1 (ALDH2 active) genotype. Conclusion: OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.

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ALDH2 genotype‐associated differences in the acute effects of alcohol on P300, psychomotor performance, and subjective response in healthy young Korean men: a double‐blind placebo‐controlled crossover study

Abstract: These results suggest that the ALDH2 polymorphism is an important factor in determining the effects of alcohol on various psychobehavioral functions.

Cited by 8 publications

References 31 publications

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea

Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults

ALDH2 Gene: Its Effects on the Neuropsychological Functions in Patients with Opioid Use Disorder Undergoing Methadone Maintenance Treatment

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