ToxSci Advance Access published online on June 30, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp143
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Roles of the Genetic Polymorphisms of Alcohol-metabolizing Enzymes on the Immunology in High-risk Drinkers
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* Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
Department of Public Healthy, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
¶ Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
1 Address for correspondence: Li-Yu Tsai, Ph.D., Professor, Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. Telephone: 886-7-3121101-2350, fax: 886-7-2370544, e-mail: tsliyu{at}kmu.edu.tw
Received April 1, 2009; revision received June 11, 2009; accepted June 17, 2009
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Abstract |
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Alcohol metabolism involves several enzymes and the individual genetic variations in the alcohol metabolism are related to the absorption, distribution and elimination of alcohol and metabolites such as acetaldehyde. Therefore, the genetic variations of alcohol-metabolizing enzymes are responsible for the different toxicity of alcohol in several organs like liver and immunological systems. The purpose of this study was to evaluate if the life styles such as drinking and smoking and the genetic variations of alcohol-metabolizing enzymes (ADH2, ALDH2, CYP2E1, and CAT) were associated with the immunological biomarkers. In this study, one hundred and five high-risk drinkers and 102 low-risk drinkers who were excluded from the immuno-related diseases and other critical diseases were enrolled to evaluate the immunological functions. Counts of white blood cells, mononuclear cells, and lymphocyte subpopulations, and liver and immunological function tests were measured. Genotypes of alcohol-metabolizing enzymes were assayed by a real-time PCR and PCR-RFLP. We found that there were significantly higher percentages of CD4+ T lymphocytes, ratios of CD4+/CD8+ and AST/ALT, activities of AST and GGT, and levels of IL-6, but lower percentages of CD8+ T lymphocytes, levels of total protein, globulin, and immunoglobulins in the high-risk drinkers. In addition, the synergistic effects of smoking and drinking on the count of WBC and mononuclear cells were found to be significant. Furthermore, there were higher OR to become high-risk drinkers in subjects with the combination of ALDH2 (*1/*1) genotype and either genotype of ADH2 or CYP2E1 than the others with other combinations of genotypes. Additionally, there were more abnormal immunological tests in the subjects with higher activity of ADH2 and lower activity of ALDH2. Our results suggested that the habits of drinking, smoking, and betel chewing, and genetic variations of alcohol metabolism were associated with the immunological biomarkers.
Key Words: high-risk drinkers; alcohol-metabolizing enzymes; genetic variations; immunology.