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

Background: Thrombocytopenia during intoxication, rebound thrombocytosis during 1 to 3 weeks of abstinence, and subsequent normalization of the platelet count are common in alcoholics. Methods: We evaluated 989 Japanese alcoholic men to identify the effects of genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B; rs1229984) and aldehyde dehydrogenase-2 (ALDH2; rs671) on platelet counts during an 8-week in-hospital abstinence period. Results: Thrombocytopenia (<15 x 10(4)/mul) was observed in 25.9% of the subjects upon admission. The platelet counts increased from 21.4 +/- 0.3 x 10(4)/mu l (mean +/- SE) to 27.6 +/- 0.3 x 10(4)/mu l, and a rebound platelet increase of >= 10 x 10(4)/mu l was observed in 28.6% of the patients during the first 2 weeks after admission. By 4 weeks, the mean platelet counts had returned to intermediate levels and remained stable thereafter. The reversible suppression and rebound increase in the platelet counts were more prominent in the slow-metabolizing ADH1B*1/*1 group than in the fast-metabolizing ADH1B*2 group. Throughout the 8 weeks, the mean platelet counts of the active ALDH2*1/*1 group were consistently lower than those in the inactive ALDH2*1/*2 group. Cirrhosis was a strong determinant of a lower platelet count. After adjustments for nongenetic factors including cirrhosis, multiple linear regression analyses showed that the ADH1B*1/*1 genotype was associated with a lower platelet count (partial regression coefficient = -1.3 x 10(4)/mu l) on the admission day, but subsequently had a positive effect on the platelet count at 1 and 2 weeks after admission (+1.5 and +3.8 x 10(4)/mu l, respectively). The ALDH2*1/*1 genotype was associated with a lower platelet count (-2.1 to -3.9 x 10(4)/mu l) consistently throughout the 8 weeks. Multiple logistic regression analyses showed that the ADH1B*1/*1 genotype increased the risk of thrombocytopenia upon admission (odds ratio [95% confidence interval] = 1.61 [1.14 to 2.27]) and of a rebound platelet increase during the first 2 weeks (3.86 [2.79 to 5.34]). The ALDH2*1/*1 genotype increased the risk of thrombocytopenia upon admission (1.73 [1.06 to 2.82]). Conclusions: In alcoholics, the ADH1B*1/*1 genotype increased the risk of thrombocytopenia upon admission and of a rebound platelet increase 2 weeks thereafter, while the ALDH2*1/*1 genotype was associated with lower platelet counts throughout the 8-week hospital stay.