Macrocytosis, Macrocytic Anemia, and Genetic Polymorphisms of Alcohol Dehydrogenase-1B and Aldehyde Dehydrogenase-2 in Japanese Alcoholic Men
Macrocytosis, Macrocytic Anemia, and Genetic Polymorphisms of Alcohol Dehydrogenase-1B and Aldehyde Dehydrogenase-2 in Japanese Alcoholic Men
复制标题
日本酗酒男性的大红细胞增多症、大红细胞性贫血以及乙醇脱氢酶 1B 和醛脱氢酶 2 的遗传多态性
DOI：
10.1111/acer.12372
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发表时间：
2014
影响因子：
3.2
通讯作者：
Maruyama K
中科院分区：
文献类型：
--
作者：
Yokoyama A;Yokoyama T;Brooks PJ;Mizukami T;Matsui T;Kimura M;Matsushita S;Higuchi S;Maruyama K
背景乙醇脱氢酶（ADH）氧化乙醇产生乙醛（AcH），乙醛脱氢酶-2（ALDH2）将其转化为乙酸。由于 ALDH2*2 等位基因编码的酶失活，大约 40% 的东亚人缺乏 ALDH2。缺乏 ALDH2 的个体因饮酒而罹患食道癌的风险显着升高。方法我们在日本酗酒男性群体 (N= 1,238) 中研究了 ALDH2*2、ADH1B*2（编码高活性 ADH）与红细胞异常之间的关系。结果大红细胞增多症（平均红细胞体积 [MCV] ≥100 fl）和大红细胞性贫血 (MCV) ≥100 fl 和血红蛋白 <13.5 g/dl）分别在 62.4% 和 24.1% 的受试者中被发现。根据 ADH1B 和 ALDH2 基因型的不同，年龄调整后的每日饮酒量没有差异。然而，大红细胞增多症和大红细胞性贫血与 ALDH2*1/*2 基因型多变量比值比密切相关（OR；95% 置信区间 [CI] = 2.85 [1.95 至 4.18] 和 3.68 [2.64 至 5.15]，分别与 ALDH2*1/*1 相比）。与 ADH1B*1/*1 和 ALDH2*1/*1 基因型组合相比，ADH1B*1/*1 和 ALDH2*1/*2 基因型组合以及 ADH1B*2 等位基因和 ALDH2*1/*2 基因型组合逐步增加了大红细胞增多症的 OR (95% CI) (1.65 [0.92 至 2.94] 和 4.07 [2.33]至 7.11]，分别为 OR = 0.015 的差异的 p）和大红细胞性贫血（分别为 2.80 [1.52 至 5.15] 和 5.32 [3.29 至 8.62]，OR = 0.045 的差异的 p）。基因型效应对更晚期红细胞异常的风险更为显着。年龄较大、吸烟和低体重指数独立增加红细胞异常的风险。饮用含有叶酸的啤酒可降低风险，而饮用缺乏叶酸的酒精饮料则不会。结论这些结果表明，酗酒者的红细胞异常可归因于高乙酰胆碱暴露和营养缺乏，叶酸可以预防这种情况。
BackgroundOxidation 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 theALDH2*2allele. ALDH2‐deficient individuals have a dramatically elevated risk of esophageal cancer from alcohol consumption.MethodsWe investigated the relationship betweenALDH2*2,ADH1B*2(encoding a highly active ADH) and erythrocyte abnormalities, in a population of Japanese alcoholic men (N= 1,238).ResultsMacrocytosis (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 theALDH2*1/*2genotype multivariate odds ratios (ORs; 95% confidence interval [CI] = 2.85 [1.95 to 4.18] and 3.68 [2.64 to 5.15], respectively, versusALDH2*1/*1). In comparison with theADH1B*1/*1andALDH2*1/*1genotype combination, theADH1B*1/*1andALDH2*1/*2genotype combination and theADH1B*2allele andALDH2*1/*2genotype 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,pfor difference in OR = 0.015) and macrocytic anemia (2.80 [1.52 to 5.15] and 5.32 [3.29 to 8.62], respectively,pfor 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.ConclusionsThese 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.