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Blood Leukocyte Counts and Genetic Polymorphisms of Alcohol Dehydrogenase‐1B and Aldehyde Dehydrogenase‐2 in Japanese Alcoholic Men
Author(s) -
Yokoyama Akira,
Brooks Philip J.,
Yokoyama Tetsuji,
Mizukami Takeshi,
Matsui Toshifumi,
Kimura Mitsuru,
Matsushita Sachio,
Higuchi Susumu,
Maruyama Katsuya
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12983
Subject(s) - aldehyde dehydrogenase , alcohol dehydrogenase , aldh2 , adh1b , alcohol , medicine , dehydrogenase , genetics , biology , biochemistry , gene , branched chain alpha keto acid dehydrogenase complex , enzyme
Background Roughly 40% of East Asians have inactive aldehyde dehydrogenase‐2 ( ALDH 2) encoded by the ALDH 2*2 allele, and 90% have highly active alcohol dehydrogenase‐1B ( ADH 1B) encoded by the ADH 1B*2 allele. Macrocytosis and macrocytic anemia in alcoholics have been associated with ADH 1B and ALDH 2 gene variants which increase acetaldehyde (AcH) levels. Methods We investigated the relationship between ADH 1B*2 , ALDH 2*2, and leukocyte counts of Japanese alcoholic men ( N = 1,661). Results After adjusting for age, drinking habits, smoking habits, body mass index, presence of liver cirrhosis, and serum levels of C‐reactive protein, we found that total and differential leukocyte counts were lower in the presence of the ALDH 2*1/*2 genotype (vs. ALDH 2*1/*1 genotype). ALDH 2*2/*2 carriers were not found in our study population. Leukocyte, granulocyte, and monocyte counts were also lower in the presence of ADH 1B*2 (vs. ADH 1B*1/*1 genotype), but the lymphocyte count was higher. The ALDH 2*1/*2 genotype was associated with leukocytopenia (<4,000/ μ l; adjusted odds ratio [95% confidence interval] = 1.89 [1.27 to 2.80]), granulocytopenia (<2,000/ μ l; 1.86 [1.22 to 2.82]), monocytopenia (<250/ μ l; 2.22 [1.49 to 3.29]), and lymphocytopenia (<1,000/ μ l; 1.93 [1.32 to 2.83]). In contrast, the ADH 1B*2 had the opposite effect on lymphocytopenia (0.65 [0.46 to 0.93]). Considering genotype effects under conditions of immune stimulation, we observed suppressive effects of ADH 1B*2 allele on leukocytosis (≥9,000/ μ l; 0.69 [0.50 to 0.97]), granulocytosis (≥6,500/ μ l; 0.66 [0.47 to 0.93]), and monocytosis (≥750/ μ l; 0.56 [0.39 to 0.79]). The ADH 1B*2 plus ALDH 2*1/*2 combination had the greatest suppressive effects on the leukocyte, granulocyte, and monocyte counts. Conclusions The total and differential blood leukocyte counts of Japanese alcoholics were strongly affected by their ADH 1B and ALDH 2 gene variants. High AcH exposure levels probably play a critical role in the suppression of blood leukocyte counts in alcoholics.