Effect of ALDH2 Genetic Polymorphism on the Adaptive Change in Alcohol Metabolism Due to Continuous Moderate Alcohol Consumption in Humans


Few studies have assessed the difference in adaptive changes of alcohol metabolism in the case of chronic alcohol consumption pertaining to the genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) in humans. To evaluate the influences of ALDH2 genotypes on changes in alcohol metabolism due to continuous alcohol intake, we conducted an intervention study by setting a continuous drinking period between two abstinence periods. The subjects in this study comprised 20 - 25-year-old males, including 15 males carrying ALDH2*1/*1 and 16 carrying ALDH2*1/*2 genotypes. Following the abstinence period of 4 weeks (from day 1 to day 28), all subjects drank commercially available beer (500 ml) every evening for 6 weeks (from day 30 to day 71) and subsequently abstained from drinking again for 4 weeks (from day 73 to day 100). The next morning, after the end of each period, drinking tests (DTs) were performed on each subject (DT1 on day 29, DT2 on day 72, and DT3 on day 101) to examine alcohol metabolism. The subjects drank shochu (a distilled alcoholic beverage), with an ethanol dose of 0.32 g/kg, within 20 minutes after overnight fasting. The alcohol elimination rate in subjects with ALDH2*1/*1 genotype was significantly higher during DT2 after the drinking period as compared with those at both DT1 and DT3 after the abstinence periods, whereas the elimination rate in subjects with ALDH2*1/*2 genotype did not change significantly during 3 DTs. However, blood acetaldehyde levels significantly decreased in subjects with both ALDH2 genotypes during DT2 as compared with those during DT1. The physiological subjective responses to alcohol also significantly decreased during DT2 in subjects with ALDH2*1/*2 genotype. Moreover, serum lipids, gamma-glutamyltransferase (GGT), and uric acid concentrations also varied between subjects with different ALDH2 genotypes due to continuous drinking. These results suggested that ALDH2 polymorphism modified adaptive changes in alcohol metabolism and physiological responses to continuous moderate alcohol consumption.

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Oshima, S. , Haseba, T. , Nemoto, A. , Siiya, S. , Kanda, T. and Ohno, Y. (2015) Effect of ALDH2 Genetic Polymorphism on the Adaptive Change in Alcohol Metabolism Due to Continuous Moderate Alcohol Consumption in Humans. Food and Nutrition Sciences, 6, 195-204. doi: 10.4236/fns.2015.62020.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Holman, C.D., English, D.R., Milne, E. and Winter, M.G. (1996) Meta-Analysis of Alcohol and All-Cause Mortality: A Validation of NHMRC Recommendations. The Medical Journal of Australia, 164, 141-145.
[2] Tsugane, S., Fahey, M.T., Sasaki, S. and Baba, S. (1999) Alcohol Consumption and All-Cause and Cancer Mortality among Middle-Aged Japanese Men: Seven-Year Follow-Up of the JPHC Study Cohort I. American Journal of Epidemiology, 150, 1201-1207.
[3] Patra, J., Taylor, B., Irving, H., Roerecke, M., Baliunas, D., Mohapatra, S. and Rehm, J. (2010) Alcohol Consumption and the Risk of Morbidity and Mortality for Different Stroke Types—A Systematic Review and Meta-Analysis. BMC Public Health, 10, 258.
[4] Ronksley, P.E., Brien, S.E., Turner, B.J., Mukamal, K.J. and Ghali, W.A. (2011) Association of Alcohol Consumption with Selected Cardiovascular Disease Outcomes: A Systematic Review and Meta-Analysis. British Medical Journal, 342, d671.
[5] Nova, E., Baccan, G.C., Veses, A., Zapatera, B. and Marcos, A. (2012) Potential Health Benefits of Moderate Alcohol Consumption. Proceedings of the Nutrition Society, 71, 307-315.
[6] Lieber, C.S. and DeCarli, L.M. (1970) Hepatic Microsomal Ethanol-Oxidizing System. In Vitro Characteristics and Adaptive Properties in Vivo. The Journal of Biological Chemistry, 245, 2505-2512.
[7] Raskin, N.H. and Sokoloff, L. (1974) Changes in Brain Alcohol Dehydrogenase Activity during Chronic Ethanol Ingestion and Withdrawal. Journal of Neurochemistry, 22, 427-434.
[8] Nomura, F., Pikkarainen, P.H., Jauhonen, P., Arai, M., Gordon, E.R., Baraona, E. and Lieber, C.S. (1983) Effect of Ethanol Administration on the Metabolism of Ethanol in Baboons. Journal of Pharmacology and Experimental Therapeutics, 227, 78-83.
[9] Aoki, Y. and Itoh, H. (1989) Effects of Alcohol Consumption on Mitochondrial Aldehyde Dehydrogenase Isoenzymes in Rat Liver. Enzyme, 41, 151-158.
[10] Kishimoto, R., Fujiwara, I., Kitayama, S., Goda, K. and Nakata, Y. (1995) Changes in Hepatic Enzyme Activities Related to Ethanol Metabolism in Mice Following Chronic Ethanol Administration. Journal of Nutritional Science and Vitaminology, 41, 527-543.
[11] Gill, K., Amit, Z. and Smith, B.R. (1996) The Regulation of Alcohol Consumption in Rats: The Role of Alcohol-Metabolizing Enzymes-Catalase and Aldehyde Dehydrogenase. Alcohol, 13, 347-353.
[12] Kozawa, S., Yukawa, N., Liu, J., Shimamoto, A., Kakizaki, E. and Fujimiya, T. (2007) Effect of Chronic Ethanol Administration on Disposition of Ethanol and Its Metabolites in Rat. Alcohol, 41, 87-93.
[13] Misra, P.S., Lefévre, A., Ishii, H., Rubin, E. and Lieber, C.S. (1971) Increase of Ethanol, Meprobamate and Pentobarbital Metabolism after Chronic Ethanol Administration in Man and in Rats. The American Journal of Medicine, 51, 346-351.
[14] Korsten, M.A., Matsuzaki, S., Feinman, L. and Lieber, C.S. (1975) High Blood Acetaldehyde Levels after Ethanol Administration. Difference between Alcoholic and Nonalcoholic Subjects. The New England Journal of Medicine, 292, 386-389.
[15] Lindros, K.O., Stowell, A., Pikkarainen, P. and Salaspuro, M. (1980) Elevated Blood Acetaldehyde in Alcoholics with Accelerated Ethanol Elimination. Pharmacology Biochemistry & Behavior, 13, 119-124.
[16] Nuutinen, H., Lindros, K.O. and Salaspuro, M. (1983) Determinants of Blood Acetaldehyde Level during Ethanol Oxidation in Chronic Alcoholics. Alcoholism: Clinical and Experimental Research, 7, 163-168.
[17] Okada, T. and Mizoi, Y. (1982) Studies on the Problem of Blood Acetaldehyde Determination in Man and Level after Alcohol Intake. Japanese Journal of Alcohol Studies and Drug Dependence, 17, 141-159.
[18] Namihira, T., Shinzato, N., Akamine, H., Maekawa, H. and Matsui, T. (2010) Influence of Nitrogen Fertilization on Tropical-Grass Silage Assessed by Ensiling Process Monitoring Using Chemical and Microbial Community Analyses. Journal of Applied Microbiology, 108, 1954-1965.
[19] Mizuno, O., Yokoyama, T. and Tsutsumi, N. (1984) The Changes of Serum Total Cholesterol, HDL-Cholesterol and Atherogenic Index in Postpartum. Nihon Sanka Fujinka Gakkai Zasshi, 36, 2593-2597.
[20] Mizoi, Y., Yamamoto, K., Ueno, Y., Fukunaga, T. and Harada, S. (1994) Involvement of Genetic Polymorphism of Alcohol and Aldehyde Dehydrogenases in Individual Variation of Alcohol Metabolism. Alcohol and Alcoholism, 29, 707-710.
[21] Gong, Z., Harada, S., Myo-Thaik-Oo and Okubo, T. (1998) Investigation for Polymorphism of ALDH2 Exon12 in Several Asian Areas. Japanese Journal of Alcohol Studies & Drug Dependence, 33, 144-150.
[22] Peng, G.S., Chen, Y.C., Tsao, T.P., Wang, M.F. and Yin, S.J. (2007) Pharmacokinetic and Pharmacodynamic Basis for Partial Protection against Alcoholism in Asians, Heterozygous for the Variant ALDH2*2 Gene Allele. Pharmacogenetics and Genomics, 17, 845-855.
[23] Sun, F., Tsuritani, I., Honda, R., Ma, Z.Y. and Yamada, Y. (1999) Association of Genetic Polymorphisms of AlcoholMetabolizing Enzymes with Excessive Alcohol Consumption in Japanese Men. Human Genetics, 105, 295-300.
[24] Oneta, C.M., Lieber, C.S., Li, J., Rüttimann, S., Schmid, B., Lattmann, J., Rosman, A.S. and Seitz, H.K. (2002) Dynamics of Cytochrome P4502E1 Activity in Man: Induction by Ethanol and Disappearance during Withdrawal Phase. Journal of Hepatology, 36, 47-52.
[25] Cornell, N.W., Crow, K.E., Leadbetter, M.G. and Veech, R.L. (1979) Alcohol and Nutrition. NIAAA Research Monograph, 2, 315-330.
[26] Crow, K.E., Braggins, T.J., Batt, R.D. and Hardman, M.J. (1982) Rat Liver Cytosolic Malate Dehydrogenase: Purification, Kinetic Properties, Role in Control of Free Cytosolic NADH Concentration. Analysis of Control of Ethanol Metabolism Using Computer Simulation. The Journal of Biological Chemistry, 257, 14217-14225.
[27] Deltour, L., Foglio, M.H. and Duester, G. (1999) Metabolic Deficiencies in Alcohol Dehydrogenase Adh1, Adh3, and Adh4 Null Mutant Mice. Overlapping Roles of Adh1 and Adh4 in Ethanol Clearance and Metabolism of Retinol to Retinoic Acid. The Journal of Biological Chemistry, 274, 16796-16801.
[28] Higuchi, S., Muramatsu, T., Shigemori, K., Saito, M., Kono, H., Dufour, M.C. and Harford, T.C. (1992) The Relationship between Low Km Aldehyde Dehydrogenase Phenotype and Drinking Behavior in Japanese. Journal of Studies on Alcohol, 53, 170-175.
[29] Tomita, Y., Haseba, T., Kurosu, M. and Watanabe, T. (1992) Effects of Chronic Ethanol Intoxication on Aldehyde Dehydrogenase in Mouse Liver. Alcohol and Alcoholism, 27, 171-180.

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