Title
Alcohol consumption and type 2 diabetes: Influence of genetic variation in alcohol dehydrogenase
Author
Beulens, J.W.J.
Rimm, E.B.
Hendriks, H.F.J.
Hu, F.B.
Manson, J.E.
Hunter, D.J.
Mukamal, K.J.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
OBJECTIVE - We sought to investigate whether a polymorphism in the alcohol dehydrogenase 1c (ADH1C) gene modifies the association between alcohol consumption and type 2 diabetes. RESEARCH DESIGN AND METHODS - In nested case-control studies of 640 women with incident diabetes and 1,000 control subjects from the Nurses' Health Study and 383 men with incident diabetes and 382 control subjects from the Health Professionals Follow-Up Study, we determined associations between the ADH1C polymorphism, alcohol consumption, and diabetes risk. RESULTS - Moderate to heavy alcohol consumption (>5 g/day for women and >10 g/day for men) was associated with a decreased risk of diabetes among women (odds ratio [OR] 0.45 [95% CI 0.33- 0.63]) but not men (1.08 [0.67-1.75]). ADH1C genotype modified the relation between alcohol consumption and diabetes for women (Pinteraction = 0.02). The number of ADH1C*2 alleles, related to a slower rate of ethanol oxidation, attenuated the lower risk of diabetes among women consuming ≥5 g alcohol/day (Ptrend = 0.002). These results were not significant among men. Results were similar in pooled analyses (Pinteraction = 0.02) with ORs for diabetes among moderate drinkers of 0.44 (95% CI 0.21- 0.94) in ADH1C*1 homozygotes, 0.65 (0.39 -1.06) for heterozygotes, and 0.78 (0.50-1.22) for ADH1C*2 homozygotes compared with those for ADH1C*1 homozygote abstainers (Ptrend = 0.02). CONCLUSIONS - ADH1C genotype modifies the association between alcohol consumption and diabetes. The ADH1C*2 allele, related to a slower oxidation rate, attenuates the lower diabetes risk among moderate to heavy drinkers. This suggests that the association between alcohol consumption and diabetes may be causal but mediated by downstream metabolites such as acetate rather than ethanol itself. © 2007 by the American Diabetes Association.
Subject
Health
Biomedical Research
alcohol dehydrogenase
alcohol dehydrogenase 1C
adult
alcohol consumption
alcohol oxidation
article
controlled study
disease association
female
gene frequency
genetic polymorphism
genotype
heterozygote
homozygote
human
major clinical study
male
morbidity
non insulin dependent diabetes mellitus
priority journal
risk factor
Adult
Alcohol Dehydrogenase
Alcohol Drinking
Case-Control Studies
Diabetes Mellitus, Type 2
Female
Gene Frequency
Genotype
Humans
Male
Middle Aged
Polymorphism, Genetic
Questionnaires
Reference Values
Smoking
Variation (Genetics)
To reference this document use:
http://resolver.tudelft.nl/uuid:df852d77-5a07-418e-99a8-bf40bd1da810
DOI
https://doi.org/10.2337/db07-0181
TNO identifier
240170
ISSN
0012-1797
Source
Diabetes, 56 (9), 2388-2394
Document type
article