Blood Leukocyte Counts and Genetic Polymorphisms of Alcohol Dehydrogenase-1B and Aldehyde Dehydrogenase-2 in Japanese Alcoholic Men.

BACKGROUND

Roughly 40% of East Asians have inactive aldehyde dehydrogenase-2 (ALDH2) encoded by the ALDH22 allele, and 90% have highly active alcohol dehydrogenase-1B (ADH1B) encoded by the ADH1B2 allele. Macrocytosis and macrocytic anemia in alcoholics have been associated with ADH1B and ALDH2 gene variants which increase acetaldehyde (AcH) levels.

METHODS

We investigated the relationship between ADH1B2, ALDH22, 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 ALDH21/2 genotype (vs. ALDH21/1 genotype). ALDH22/2 carriers were not found in our study population. Leukocyte, granulocyte, and monocyte counts were also lower in the presence of ADH1B2 (vs. ADH1B1/1 genotype), but the lymphocyte count was higher. The ALDH21/2 genotype was associated with leukocytopenia (<4,000/μl; adjusted odds ratio [95% confidence interval] = 1.89 [1.27 to 2.80]), granulocytopenia (<2,000/μl; 1.86 [1.22 to 2.82]), monocytopenia (<250/μl; 2.22 [1.49 to 3.29]), and lymphocytopenia (<1,000/μl; 1.93 [1.32 to 2.83]). In contrast, the ADH1B2 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 ADH1B2 allele on leukocytosis (≥9,000/μl; 0.69 [0.50 to 0.97]), granulocytosis (≥6,500/μl; 0.66 [0.47 to 0.93]), and monocytosis (≥750/μl; 0.56 [0.39 to 0.79]). The ADH1B2 plus ALDH2*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 ADH1B and ALDH2 gene variants. High AcH exposure levels probably play a critical role in the suppression of blood leukocyte counts in alcoholics.