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

Abstract

Thrombocytopenia during intoxication, rebound thrombocytosis during 1 to 3weeks of abstinence, and subsequent normalization of the platelet count are common in alcoholics. 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. Thrombocytopenia (<15×104 /μl) was observed in 25.9% of the subjects upon admission. The platelet counts increased from 21.4±0.3×104 /μl (mean±SE) to 27.6±0.3×104 /μl, and a rebound platelet increase of ≥10×104 /μl was observed in 28.6% of the patients during the first 2weeks after admission. By 4weeks, 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 8weeks, 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=-1.3×104 /μl) on the admission day, but subsequently had a positive effect on the platelet count at 1 and 2weeks after admission (+1.5 and +3.8×104 /μl, respectively). The ALDH2*1/*1 genotype was associated with a lower platelet count (-2.1 to -3.9×104 /μl) consistently throughout the 8weeks. 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 2weeks (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]). In alcoholics, the ADH1B*1/*1 genotype increased the risk of thrombocytopenia upon admission and of a rebound platelet increase 2weeks thereafter, while the ALDH2*1/*1 genotype was associated with lower platelet counts throughout the 8-week hospital stay.