Macrocytosis, Macrocytic Anemia, and Genetic Polymorphisms of Alcohol Dehydrogenase‐1B and Aldehyde Dehydrogenase‐2 in Japanese Alcoholic Men. (3rd March 2014)

• Record Type: Journal Article
• Authors: Yokoyama, Akira; Yokoyama, Tetsuji; Brooks, Philip J.; Mizukami, Takeshi; Matsui, Toshifumi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya
• Is Part Of: Alcoholism. Volume 38:Number 5(2014:May)
• Page Start: 1237
• Page End: 1246
• Publication Date: 2014-03-03
• Subjects: Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.12372
• Languages: English
• ISSNs: 0145-6008

Abstract

<abstract abstract-type="main" id="acer12372-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="acer12372-sec-0001" sec-type="section"> <title>Background</title> <p>Oxidation of ethanol by alcohol dehydrogenase (ADH) generates acetaldehyde (AcH), which is converted to acetate by aldehyde dehydrogenase‐2 (ALDH2). Roughly 40% of East Asians are ALDH2‐deficient due to an inactive enzyme encoded by the <italic>ALDH2*2</italic> allele. ALDH2‐deficient individuals have a dramatically elevated risk of esophageal cancer from alcohol consumption.</p> </sec> <sec id="acer12372-sec-0002" sec-type="section"> <title>Methods</title> <p>We investigated the relationship between <italic>ALDH2*2</italic>, <italic> ADH1B*2</italic> (encoding a highly active ADH) and erythrocyte abnormalities, in a population of Japanese alcoholic men (<italic>N</italic> = 1, 238).</p> </sec> <sec id="acer12372-sec-0003" sec-type="section"> <title>Results</title> <p>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 ADH1B and ALDH2 genotypes. However, macrocytosis and macrocytic anemia were strongly associated with the <italic>ALDH2*1/*2</italic> genotype multivariate odds ratios (ORs; 95% confidence interval [CI] = 2.85 [1.95 to 4.18] and 3.68 [2.64 to 5.15], respectively, versus <italic>ALDH2*1/*1</italic>). In comparison with the <italic>ADH1B*1/*1</italic> and <italic>ALDH2*1/*1</italic> genotype combination, the <italic>ADH1B*1/*1</italic> and <italic>ALDH2*1/*2</italic> genotype combination and the <italic>ADH1B*2</italic> allele and <italic>ALDH2*1/*2</italic> genotype combination increased stepwise the ORs (95% CI) for macrocytosis (1.65 [0.92 to 2.94] and 4.07 [2.33 to 7.11], respectively, <italic>p</italic> 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, <italic>p</italic> 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.</p> </sec> <sec id="acer12372-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>