Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure?
BACKGROUND
Several cross-sectional studies have examined whether the relationship between alcohol consumption and blood pressure (alcohol-BP relationship) differs among individuals with different aldehyde dehydrogenase-2 (ALDH2) genotypes, but few studies have examined the association with alcohol dehydrogenase-2 (ADH2), and those have yielded inconsistent results. We examined the potential modulatory effects of ADH2 and ALDH2 genotypes on the alcohol-BP relationship in a cross-sectional sample of a Japanese rural community.


RESULTS
The study subjects were 335 randomly selected men aged 40-69 years, who lived in Shiso, a Japanese rural county, in 1999 or 2000. The genetic polymorphisms of ADH2 and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The frequencies of ADH21/21 (wild-type), 21/22 (superactive heterozygotes), and 22/22 (superactive homozygotes) were 8.4, 34.9 and 56.7%, respectively; and those of ALDH21/21 (wild-type), 21/22 (inactive heterozygotes), and 22/22 (inactive homozygotes) were 52.8, 40.9, and 6.3%, respectively. A multiple linear regression analysis showed that the relationship between alcohol consumption and diastolic blood pressure was significantly stronger in men with ADH21/21 than those with ADH21/22 or 22/22 (adjusted regression coefficient = 0.0392 versus 0.0113 mmHg for + 1 g ethanol/week, P for difference in slope = 0.018). The strength of the alcohol-BP relationship was similar in all of the ALDH2 genotype groups.


CONCLUSIONS
The alcohol-BP relationship was significantly stronger in men with ADH21/21 than in men with ADH21/22 or 22/22 in this Japanese rural population. This finding was exactly the opposite of what one previous study suggested.
Saito
Kyoko
K
Department of Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. kyon@niph.go.jp
Yokoyama
Tetsuji
T
Yoshiike
Nobuo
N
Date
Chigusa
C
Yamamoto
Akio
A
Muramatsu
Masaaki
M
Tanaka
Heizo
H
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001794:Blood Pressure / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics; D003430:Cross-Sectional Studies; D000431:Ethanol / Q000493:pharmacokinetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012424:Rural Population
D002492:Central Nervous System Depressants; D000431:Ethanol; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial