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ADH genotype does not modify the effects of alcohol on high-density lipoprotein
John B Whitfield1, Martin E O'Brien, Brian N Nightingale
1Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia. John.Whitfield@email.cs.nsw.gov.au
Insights
Alcohol consumption increases high-density lipoprotein (HDL) levels, potentially reducing cardiovascular disease risk. However, alcohol dehydrogenase (ADH) genotypes ADH2 and ADH3 do not appear to modify this HDL response to alcohol intake.
Area of Science:
- Cardiovascular disease research
- Genetics and personalized medicine
- Alcohol metabolism studies
Background:
- Moderate alcohol consumption is linked to reduced cardiovascular disease mortality.
- This benefit is partly attributed to increased high-density lipoprotein (HDL) levels.
- Alcohol dehydrogenase (ADH) genotypes, specifically ADH3, have been proposed to influence HDL response to alcohol.
Purpose of the Study:
- To investigate the impact of ADH2 and ADH3 genotypes on HDL components in response to habitual alcohol consumption.
- To determine if alcohol dehydrogenase genotype modifies the relationship between alcohol intake and HDL levels.
Main Methods:
- Genotyping of adult subjects for ADH2 and ADH3.
- Measurement of plasma HDL cholesterol, apolipoprotein A-I, and apolipoprotein A-II.
- Statistical analysis of HDL components and a derived factor score in relation to alcohol intake across different ADH2 and ADH3 genotype groups.
Main Results:
- All measured HDL components showed an increase with rising alcohol consumption (0-4 drinks/day).
- No significant interactions were found between alcohol consumption levels and ADH2 or ADH3 genotypes.
- The study did not find evidence supporting genotype modification of HDL response.
Conclusions:
- The hypothesis that alcohol dehydrogenase genotype influences alcohol's effect on plasma HDL concentration is not supported by this study's findings.
- Alcohol's impact on HDL appears independent of ADH2 and ADH3 genotypes within the studied range of consumption.
- Further research may be needed to explore other genetic or metabolic factors influencing alcohol-related cardiovascular benefits.
Background:
Alcohol consumption has beneficial effects on mortality which are mainly due to reduction in cardiovascular disease. These are believed to be due, at least in part, to the increase in plasma high-density lipoprotein (HDL) which is associated with alcohol consumption. It has been proposed that ADH3 genotype modifies the relationships between alcohol intake and cardiovascular disease by altering the HDL response to alcohol. The aim of this paper was to test for effects of ADH2 and ADH3 genotypes on the response of HDL components to habitual alcohol consumption.
Methods:
Adult male and female subjects were genotyped for ADH2 and ADH3; and plasma HDL cholesterol, apolipoprotein A-I, and apolipoprotein A-II were measured. Nine hundred one subjects had both ADH2 and ADH3 genotypes and HDL cholesterol results, while 753 had both genotypes and all three lipid results. The effect of alcohol intake on the three measured HDL components, and a factor score derived from them, was estimated for each of the ADH2 and ADH3 genotype groups.
Results:
All the measured components of HDL increased with increasing alcohol consumption over the range of intakes studied, 0-4 drinks per day. There were no significant interactions between alcohol consumption and ADH2 or ADH3 genotypes.
Conclusions:
The concept that alcohol dehydrogenase genotype and alcohol metabolic rate modify the effects of alcohol on plasma HDL concentration is not supported by our results.