Premium
Macrocytosis, Macrocytic Anemia, and Genetic Polymorphisms of Alcohol Dehydrogenase‐1 B and Aldehyde Dehydrogenase‐2 in J apanese Alcoholic Men
Author(s) -
Yokoyama Akira,
Yokoyama Tetsuji,
Brooks Philip J.,
Mizukami Takeshi,
Matsui Toshifumi,
Kimura Mitsuru,
Matsushita Sachio,
Higuchi Susumu,
Maruyama Katsuya
Publication year - 2014
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.12372
Subject(s) - aldh2 , adh1b , mean corpuscular volume , macrocytosis , medicine , aldehyde dehydrogenase , alcohol dehydrogenase , gastroenterology , anemia , odds ratio , population , hematocrit , alcohol , biology , genetics , biochemistry , branched chain alpha keto acid dehydrogenase complex , dehydrogenase , environmental health , gene , enzyme
Background Oxidation of ethanol by alcohol dehydrogenase ( ADH ) generates acetaldehyde (AcH), which is converted to acetate by aldehyde dehydrogenase‐2 ( ALDH 2). Roughly 40% of E ast A sians are ALDH 2‐deficient due to an inactive enzyme encoded by the ALDH 2*2 allele. ALDH 2‐deficient individuals have a dramatically elevated risk of esophageal cancer from alcohol consumption. Methods We investigated the relationship between ALDH 2*2 , ADH 1 B *2 (encoding a highly active ADH ) and erythrocyte abnormalities, in a population of Japanese alcoholic men ( N = 1,238). Results Macrocytosis ( mean corpuscular volume [MCV] ≥100 fl) and macrocytic anemia ( MCV ≥100 fl and hemoglobin <13.5 g/dl) were found in 62.4 and 24.1% of the subjects, respectively. Age‐adjusted daily alcohol consumption did not differ according to ADH 1 B and ALDH 2 genotypes. However, macrocytosis and macrocytic anemia were strongly associated with the ALDH 2*1/*2 genotype multivariate odds ratios ( OR s; 95% confidence interval [CI] = 2.85 [1.95 to 4.18] and 3.68 [2.64 to 5.15], respectively, versus ALDH 2*1/*1 ). In comparison with the ADH 1 B *1/*1 and ALDH 2*1/*1 genotype combination, the ADH 1 B *1/*1 and ALDH 2*1/*2 genotype combination and the ADH 1 B *2 allele and ALDH 2*1/*2 genotype combination increased stepwise the OR s (95% CI ) for macrocytosis (1.65 [0.92 to 2.94] and 4.07 [2.33 to 7.11], respectively, p for difference in OR = 0.015) and macrocytic anemia (2.80 [1.52 to 5.15] and 5.32 [3.29 to 8.62], respectively, p for difference in OR = 0.045). Genotype effects were more prominent on the risks of the more advanced erythrocyte abnormalities. Older age, cigarette smoking, and low body mass index independently increased the risks of the erythrocyte abnormalities. Consumption of beer, which contains folate, decreased the risks, whereas consumption of alcoholic beverages lacking folate did not. Conclusions These results suggest that the erythrocyte abnormalities in alcoholics are attributable to high AcH exposure as well as to nutritional deficiencies and may be prevented by folate.