Yokoyama Masako, Yokoyama Akira, Yokoyama Tetsuji, Hamana Genichi, Funazu Kazuo, Kondo Shuji, Yamashita Takeshi, Yoshimizu Haruko, Nakamura Haruo
Mitsukoshi Health and Welfare Foundation, Tokyo, Japan.
Alcohol Clin Exp Res. 2003 Sep;27(9):1395-401. doi: 10.1097/01.ALC.0000085589.47243.8D.
Increased mean corpuscular volume (MCV) is common in alcohol abusers and alcoholics. MCV is higher in Japanese heavy drinkers with inactive aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH21/22 than among those with active ALDH2 encoded by ALDH21/21. Inactive ALDH2 dramatically increases blood acetaldehyde levels after alcohol intake. Because moderate and heavy drinkers with ALDH21/22 have very high risks for esophageal cancer, MCV might serve as an indicator of these high-risk drinkers.
In this investigation of the association of red cell values with the ALDH2 genotype and possible confounding factors, the drinking, smoking, and dietary habits reported on a structured questionnaire by 163 Japanese working men were subjected to multivariate analyses.
Aging, lower body mass index (BMI), more alcohol consumption, and more smoking were positively associated with increased MCV. Among moderate to heavy drinkers (>or=9 units/week; 1 unit = 22 g of ethanol), both MCV and mean corpuscular hemoglobin were higher and the red cell count was lower in those with ADLH21/22 than in those with ALDH21/21. Multiple linear regression analysis after adjustment for age, BMI, and smoking revealed that a positive relationship between the amount of drinking and MCV but inverse relationships for drinking and red cell count, as well as hemoglobin and hematocrit values, were significantly stronger for men with ALDH21/22 than for those with ALDH21/21, demonstrating a gene-environment interaction. Drinking accounted for 19.9% of interindividual MCV variance among men with ALDH21/22 but for only 1.3% of variance among those with ALDH21/21. Age, BMI, drinking, and smoking accounted for 52.1 and 34.7% of the variation among those with ALDH21/22 and ALDH21/21, respectively. Macrocytosis (MCV >or=100.0 fl) was observed in 18 subjects (11.0%), and use of macrocytosis as a biomarker of moderate to heavy drinkers with ALDH21/2*2 had a sensitivity of 54.5% (6 of 11) and a specificity of 92.1% (140 of 152).
Alcohol-related red cell value changes associated with inactive ALDH2 in Japanese men suggest the importance of acetaldehyde's role in increasing MCV and the potential for using MCV as a marker for high-risk drinkers for esophageal cancer.
平均红细胞体积（MCV）升高在酗酒者和酒精成瘾者中很常见。在由ALDH21/22编码的醛脱氢酶-2（ALDH2）无活性的日本重度饮酒者中，MCV高于由ALDH21/21编码的具有活性ALDH2的饮酒者。饮酒后，无活性的ALDH2会显著提高血液中乙醛水平。由于携带ALDH21/22的中度和重度饮酒者患食管癌的风险非常高，MCV可能作为这些高危饮酒者的一个指标。
在这项关于红细胞值与ALDH2基因型及可能的混杂因素之间关联的研究中，对163名日本在职男性通过结构化问卷报告的饮酒、吸烟和饮食习惯进行了多变量分析。
年龄增长、较低的体重指数（BMI）、更多的酒精摄入量和更多的吸烟量与MCV升高呈正相关。在中度至重度饮酒者（≥9单位/周；1单位 = 22克乙醇）中，携带ADLH21/22的人比携带ALDH21/21的人MCV和平均红细胞血红蛋白更高，而红细胞计数更低。在对年龄、BMI和吸烟进行调整后的多元线性回归分析显示，饮酒量与MCV之间的正相关关系，以及饮酒量与红细胞计数、血红蛋白和血细胞比容值之间的负相关关系，在携带ALDH21/22的男性中比携带ALDH21/21的男性中显著更强，表明存在基因 - 环境相互作用。饮酒在携带ALDH21/22的男性个体间MCV差异中占19.9%，而在携带ALDH21/21的男性中仅占1.3%。年龄、BMI、饮酒和吸烟分别在携带ALDH21/22和ALDH21/21的人群中占变异的52.1%和34.7%。18名受试者（11.0%）出现大细胞性贫血（MCV≥100.0飞升），将大细胞性贫血用作携带ALDH21/2*2的中度至重度饮酒者的生物标志物，其敏感性为54.5%（11例中的6例），特异性为92.1%（152例中的140例）。
日本男性中与无活性ALDH2相关的酒精相关红细胞值变化表明乙醛在增加MCV方面的作用很重要，以及将MCV用作食管癌高危饮酒者标志物的潜力。
