Alcohol drinking frequency is more directly associated with alcohol use disorder than alcohol metabolizing enzymes among male Japanese

Abstract

The development of alcohol use disorder (AUD) is related to various social, economic, cultural, environmental and hereditary factors. Several potential risk factors have been proposed for AUD in addition to alcohol consumption, including alcohol dehydrogenase2 (ADH2), acetaldehyde dehydrogenase2 (ALDH2), marital status, educational, occupational or past medical history (e.g. diabetes mellitus, hypertension, lung, digestive tract, or chronic liver disease) or smoking habits. The present study was performed to investigate the relationship between the aforementioned potential risk factors and AUD in Japan. A case-control study was performed on 153 male Japanese AUD patients and age-, gender-, or other confounder-matched controls to investigate the relation multivariately between ADH2 , ALDH2 or alcohol drinking and AUD. Genomic DNA were extracted from nail clippings by the guanidium method, and genotyping of ADH2 and ALDH2 were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Univariate analyses by the conditional logistic regression model revealed statistically significant odds ratios due to ADH2*1/1 genotype, ALDH2*1/1 genotype, middle school as the final school attended, longest occupations as farmers, fishermen, craftsmen, miners, production process or construction workers, and past histories of chronic liver disease and AUD. However, multivariate analyses under a hierarchically well-formulated model strategy with interaction and confounding assessment indicated that (i) heavy alcohol intake was a significant risk factor (odds ratio per 1.0 g of daily ethanol intake; 1.096, 95% confidence interval; 1.026-1.171) for developing AUD after adjusting for other confounders; and (ii) ADH2*1/1 genotype and ALDH2*1/1 genotype were not risk factors after adjusting for daily ethanol intake and other confounders. The present study shows that AUD was more directly and strongly associated with alcohol drinking than with alcohol metabolizing enzymes among male Japanese.

CLINICAL STUDY: Physical health problems among patients seeking treatment for alcohol use disorders: a study in six European cities

“…Previous studies have reported that frequency of alcohol use (Nishiyori et al . 2005) and quantity of alcohol consumption (Becker et al .…”

Analysis of ADH1B Arg47His, ALDH2 Glu487Lys, and CYP4502E1 polymorphisms in gastric cancer risk and interaction with environmental factors

“…In individuals carrying the AA genotypes of both polymorphisms, plasma levels of acetaldehyde are relatively high and this compound persists in the body over long periods. Such individuals are therefore at an increased risk of developing cancer in comparison to those carrying wild-type sequences (Nishiyori et al, 2005;Yang et al, 2005;Wang et al, 2011). CYP4502E1 encodes an important phase I biological metabolism enzyme (dimethylnitrosamine-demethylase) that can activate the nitrosamines and anilines in the human body.…”

Alcohol dehydrogenase 1B genotype and fetal alcohol syndrome: a HuGE minireview

“…This association has been seen for ADH1B*2 most clearly in Asians. 16,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] An association has also been reported in Jews, 44 Hispanics, 17,45 and non-Hispanic whites, 17,43,[46][47][48][49] as well as in a metaanalysis. 50 However, not all studies have found a correlation.…”