Relationship between Genetic Polymorphisms of Alcohol-metabolizing Enzymes and Changes in Risk Factors for Coronary Heart Disease Associated with Alcohol Consumption

Abstract

Background: There are large individual variations in the responses of risk factors for coronary heart disease to alcohol consumption. To clarify the factors responsible for these individual variations, we studied the relationship between blood pressure, serum lipids, and uric acid and the genetic polymorphisms of alcohol dehydrogenase (ADH) 2 and aldehyde dehydrogenase (ALDH) 2 in alcohol drinkers. Methods: We examined 133 male workers who drank >300 g of alcohol per week. Information regarding lifestyle habits was obtained by questionnaire. The ADH2 genotype was determined by PCR and subsequent digestion with MaeIII. The ALDH2 genotype was determined based on amplified product length polymorphisms. Results: When the workers were divided into three groups: the ADH21/21, ADH21/22, and ADH22/22 groups, the mean triglycerides and γ-glutamyl transpeptidase concentrations were significantly higher in the ADH22/22 group than in the ADH21/21 group. In addition, multiple logistic regression analysis showed that the frequencies of individuals whose systolic blood pressure, triglycerides, and uric acid values were in the highest one third were significantly higher in the ADH22/22 group than in the ADH21/21 group. In contrast, no difference was observed between the ALDH21/21 and (ALDH21/22 + ALDH22/22) groups with regard to the mean value of any variable and to the frequency of individuals with any variable value in the highest one third. Conclusion: Individuals with the ADH21/21 genotype might suffer fewer negative effects of drinking.

Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary syndrome

“…Our results showed that ALDH2 mutant was associated with lower HDL-C levels, which was consistent with a study in Japanese men [5]. However, another study in Japanese suggested that there was no association between ALDH2 mutant and HDL-C levels [22], and our study showed that the association of ALDH2 mutant and ACS was still significant after HDL-C was included for logistic analysis. These results suggest that the relationship between ALDH2 gene and HDL-C should be further investigated in studies with larger sample.…”

The Association of ADH and ALDH Gene Variants With Alcohol Drinking Habits and Cardiovascular Disease Risk Factors

“…In addition an interaction between ADH1c and the level of alcohol consumption in relation to HDL has been reported in several studies (Hines et al., 2001, 2005) although not in all (Whitfield et al., 2003; Younis et al., 2005). The ADH1b has been associated with blood pressure, triglycerides, and uric acid in one study of Japanese (Hashimoto et al., 2002b), whereas another study on Europeans found no relation to HDL (Whitfield et al., 2003). In addition these, ADH variants have been related to other outcomes such as cancer in European populations (Hashibe et al., 2008; Homann et al., 2006).…”

ADH Genotype Does Not Modify the Effects of Alcohol on High‐Density Lipoprotein

“…This reasoning should also apply to genetic variation at the ADH2 locus, where the in vitro enzyme activities associated with ADH2*2 and ADH2*3 are substantially greater than for ADH2*1. In another report (Hashimoto et al, 2002) on ADH effects on several cardiovascular risk factors in moderate to heavy drinkers, the effects of ADH2 variation were studied. Among these Japanese subjects, there was a comparatively high frequency of the ADH2*2 allele.…”

“…The report that ADH3 (ADH1C) genotype affects both cardiovascular mortality and HDL responses to alcohol use (Hines et al, 2001) is of particular interest because it suggests that alcohol metabolism, rather than any particular type of alcoholic beverage or individual characteristics related to drinking habits, leads to the observed effects. However, a more recent paper that classified drinkers by ADH2 (ADH1B) type (Hashimoto et al, 2002) reported no significant difference in HDL by genotype, and the in vitro properties of ADH2 enzymes suggest that any effect should be larger than for ADH3.…”