Gender differences in the genetic risk for alcohol dependence--the results of a pharmacogenetic study in Korean alcoholics.

The genotype frequencies of the ADH2 and ALDH2 gene polymorphisms as well as the A118G polymorphism of the mu opioid receptor gene (OPRM1) in Korean men and women with alcohol dependence (AD) were compared with those of normal healthy (NH) Korean men and women at a low risk for alcoholism. 1) The frequencies of the ADH2*1/1 and ALDH2*1/1 genotypes were significantly higher in the AD men than in the NH men. However, the frequencies of the ADH2*1/1 and ALDH2*1/2 or 2/2 genotypes were significantly higher in the AD women than in the NH women. And 92% of AD men have the ALDH2*1/1 genotype, while 61% of AD women have the ADH2*1/1 genotype. 2) A gender comparison of the AD and NH groups revealed a significantly higher frequency of the A/G or G/G (hereinafter G carrier) genotypes of the OPRM1 A118G polymorphism in AD women. but not in AD men. These results suggest that, while the risk of alcoholism in Korean men is predominantly affected by the presence of the ALDH2 1/1 genotype, the risk of alcoholism in Korean women is primarily associated with the ADH2 1/1 genotype and G carrier genotype of the OPRM1 A118G polymorphism. It appears that these gender differences make it easier for alcoholic women to become intoxicated, thus making them more vulnerable to developing alcoholism. Our finding that naltrexone treatment was more effective in terms of time to first relapse in Korean AD men with the G carrier genotype than in those with the A/A genotype suggests that there is the possibility that naltrexone is more effective in the treatment of Korean AD women AD with the G carrier genotype.