Association of ALDH2 Genotypes and Alcohol Intake with Dietary Patterns: The Bunkyo Health Study.

Dietary habits are associated with various diseases and assessed by dietary patterns (DPs). Since the ALDH2 genotype is correlated with alcohol and several food preferences, this genotype is probably associated with DPs. In this cross-sectional study of 1612 elderly adults, we investigated the effects of the ALDH2 genotype on DPs and the mediating role of alcohol intake. We identified the ALDH2 genotype and conducted a dietary history survey, then used principal component analysis to determine DPs for each gender. We performed multiple regression analysis to determine the independent contribution of the ALDH2 genotype and alcohol intake to DP scores. We identified three DPs: the "Japanese side dish type" (DP1), the "Japanese dish with alcohol type" (DP2), and the "Western dish with alcohol type" (DP3). In men, the single nucleotide polymorphism ALDH2 rs671 was significantly associated with all DP scores. When alcohol intake was added as a covariate, ALDH2 rs671 was still significantly correlated with the DP2 score but not with the DP1 or DP3 score, and alcohol intake was significantly correlated with all DP scores. In women, ALDH2 rs671 was significantly associated with the DP2 and DP3 scores; however, after adding alcohol intake as a covariate, these associations disappeared, and alcohol intake significantly correlated with all DP scores. In conclusion, the ALDH2 genotype was associated with several DPs in elderly adults, but most associations were mediated by alcohol intake.

The Defective Allele of Aldehyde Dehydrogenase 2 Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma.

Background: The Aldehyde dehydrogenase 2 (ALDH2) mutant genotypes contain an allele encoding defective ALDH2 with reduced efficacy of alcohol metabolism leading to accumulation of highly toxic and carcinogenic acetaldehyde. It can induce unpleasant "Asian flush syndrome" and associate with increased risk of cancers. However, to date, little is known about ALDH2 genotypes in relation to the postoperative prognosis of hepatocellular carcinoma (HCC). Methods: From 2002 to 2012, 419 HCC patients receiving surgical resection of HCC were enrolled for ALDH2-rs671 genotyping and outcome correlation. Results: Of the patients included, 202 were ALDH2-rs671 "GG" (wild type) and 217 were mutant (defective) "AA" + "GA" genotype. Kaplan-Meier analysis indicated that "GG" genotype significantly associated with shorter metastasis-free (P = 0.034) and overall (P = 0.005) survival, but not recurrence-free survival (P = 0.281). Univariate followed by multivariate Cox proportional hazard analysis showed that "GG" genotype was an independent clinical predictor for shorter time-to-distant metastasis (adjusted P = 0.019) and shorter overall survival (adjusted P = 0.001). Subgroup analysis showed that in patients with negative hepatitis B surface antigen, Edmonson's histology grade < 3, and aspartate transaminase > alanine transaminase, the ALDH2-rs671-GG genotype was associated with both shorter time-to-metastasis and shorter overall survival. Conclusions: HCC patients carrying a defective allele of ALDH2 had a favorable postoperative outcome.

Impact of Genetic Variation in Aldehyde Dehydrogenase 2 and Alcohol Consumption on Coronary Artery Lesions in Chinese Patients with Stable Coronary Artery Disease.

The aim of this study is to investigate the impact of aldehyde dehydrogenase 2 (ALDH2) genotype and alcohol consumption on coronary artery lesions in Chinese patients with stable coronary artery disease (CAD). A total of 753 Chinese patients (73.6% male) diagnosed with stable CAD by coronary angiography were included in the sample. The frequency of the mutated type ALDH2*2 (including ALDH2*1/*2 and ALDH2*2/*2) was 44.1% in CAD patients. The mutated ALDH2 carriers were more susceptible to multivessel lesions. Low to moderate alcohol consumption is related to higher plasma HDL-C level and fewer coronary artery lesions in CAD patients with ALDH2 wild genotype, while these effects were not observed in CAD patients with ALDH2 mutated genotype. Furthermore, we divided the mutated group into heterozygous and homozygous subgroups, and no obvious relationships were observed among drinking and HDL-C and coronary lesions. To explore the metabolic effects of ALDH2 modified by alcohol, we examined the impact of ALDH2 genotype and alcohol intake on HDL-C levels in ALDH2 wild type and knockout mice. The results showed HDL-C levels were significantly higher post low to moderate alcohol consumption in wild type rather than in knockout mice. CAD patients with mutated ALDH2 genotype are inclined to suffer with coronary artery lesions than wild type subjects. Low to moderate ethanol intake contributes to fewer multivessel lesions in CAD patients with ALDH2 wild type, which might be related to higher HDL-C level.

Acute Alcohol Responses and Personality Traits by Aldehyde Dehydrogenase 2 Genotype Variances in Patients with Alcohol Dependence

OBJECTIVES: The purpose of this study is to evaluate the pathophysiology of alcoholics by investigating the differences in frequency of Aldehyde Dehydrogenase 2(ALDH2) genotypes and ALDH2 alleles between patients with alcohol dependence and controls, and the differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances. METHODS: The authors selected 98 patients with alcohol dependence and 53 controls. Self-report questionnaires for acute reponses after alcohol ingestion, the AUI(Alcohol Use Inventory), and the NEO-PI-R(NEO Personality Inventory Revised) were given to all patients with alcohol dependence. ALDH2 genotypes were typed with Mbo II RFLP(Restriction Fragment Length Polymorphism) method in 53 controls and 98 patients with alcohol dependence. The authors divided alcoholic patients into two groups according to the presence of variant ALDH22 allele; normal ALDH2 alcoholics(N=87) and variant ALDH2 alcoholics(N=11). RESULTS: 1) The genotypic frequencies of subjects with ALDH21/1 were higher and those with ALDH21/2 and ALDH22/2 were lower in patients than in controls. 2) Alcohol dependence could be found in ALDH22/2 homozygote individuals. 3) Variant ALDH2 alcoholics had more family problems in the AUI than normal ALDH2 alcoholics. 4) Variant ALDH2 alcoholics experienced more flushing and cardiovascular responses after alcohol ingestion than normal ALDH2 alcoholics. 5) Variant ALDH2 alcoholics had less altruistic personality traits in the NEO-PI-R than normal ALDH2 alcoholics. 6) Variant ALDH2 alcoholics tended to have more tolerance to alcohol than normal ALDH2 alcoholics. CONCLUSION: Variant ALDH22 allele might play a protective role in the pathogenesis of alcohol dependence and there were several significant differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances.