The Influence of ADH1B, ALDH2 Activities and Their Combination on Drinking Behaviors of Korean Young Adults

OBJECTIVES: It is well-known that Korean people show distinctive drinking behaviors depending on the gene polymorphisms of alcohol metabolizing enzymes. This study examined the gene polymorphisms of ALDH2 and ADH1B and their combination on the drinking behaviors of Korean young adults. METHODS: Through a follow-up survey performed for a cohort consisting of 551 university freshmen for six years, the authors attempted to identify genetic factors affecting drinking behaviors. In 2000, drinking behaviors and scores of CAGE questionnaires were assessed and ALDH2 gene polymorphism was determined with PCR-RFLP. In 2006(n= 150), AUDIT-K was assessed in addition to the above and gene polymorphism of ADH1B was determined through SNaPshottrade mark method. RESULTS: While ALDH2*2 allele was associated with increased degree of drinking in 2000 and 2006. When both enzymes were active, the possibility to be classified into the risk group for alcohol dependence such as AUDIT-K(>12), and CAGE(>2) was high. CONCLUSION: The ALDH2 genotype had a significant effect on drinking behavior and degree of drinking during early adulthood. However, the combination of the active form of ADH1B and the active form of ALDH2 can be risk factor for problem drinking.

The Genetic Factors Affecting Drinking Behaviors of Korean Young Adults with Variant Aldehyde Dehydrogenase 2 Genotype

OBJECTIVE: We determined whether aldehyde dehydrogenase 2 (ALDH2) activity alters the way in which drinking behaviors are affected by gene polymorphisms of other alcohol-metabolizing enzymes and serotonin-related proteins. METHODS: Through a follow-up survey with a cohort comprising 551 university freshmen over a period of 6 years, we examined the genetic factors affecting drinking behaviors. In 2000, drinking behaviors were assessed and tryptophan hydroxylase (TPH) and ALDH2 gene polymorphisms were determined. Drinking behaviors were repeated in 2006 (n=150), and the gene polymorphisms of ADH1B, ADH1C, CYP2E1, 5-HTR2A 1438A/G, and 5-HTR2A IVS2 were also determined. RESULTS: In 2000, the variant and wild-type ALDH2 groups exhibited little difference in terms of drinking frequency and problem drinking. Furthermore, some genotypes influenced only the variant group: ADH1B*2/*2 was associated with a lower drinking frequency, and CYP2E1 c2 allele was associated with an increased risk of problem drinking. In 2006, drinking frequency and risk of problem drinking were significantly lower in the variant group than in the wild-type group. However, the TPH AA genotype disturbed that difference, meaning that the subjects in the variant group had developed a similar level of risk of problem drinking to that in the wild-type group. CONCLUSION: Korean university freshmen who were identified as a variant group drank as frequently as those in the wild-type group. For the subsequent 6 years they drank less frequently, thus decreasing the risk of problem drinking. However, that frequency drop was interrupted in those with gene polymorphisms such as ADH1B*1, CYP2E1 c2, and TPH A.

The Effect of ADH1B and NQO2 Polymorphisms on the Age of Onset of Alcohol Dependence and Alcohol Withdrawal Symptoms / 신경정신의학

OBJECTIVES: We hypothesized that polymorphisms of ADH1B and NQO2 could have an effect on the onset of alcohol dependence and withdrawal symptoms. METHODS: PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism) were used to analyze genetic polymorphisms of ADH1B and NQO2 in 194 male patients with alcohol dependence (AD) and 152 healthy comparisons. The AD were classified into the early and late onset groups with the onset age of 25. Alcohol withdrawal symptoms were measured by Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar). RESULTS: 1) Alcohol dehydrogenase 1B gene : There was no difference in genotype distribution between the patients group and the control group. However, the frequency of ADH1B*2 allele in late-onset alcohol dependence was higher compared to the early-onset group. 2) NRH-quinone oxidoreductase 2 (NQO2) : The patients group had higher frequency of D allele than the healthy comparisons. In patients group, the frequency of the D allele in the late-onset group was higher than the early-onset group. 3) CIWA-Ar scale : There was no difference in the CIWA-Ar scale between the genetic polymorphisms of ADH1B. However, the patients with D allele of NQO2 showed significantly higher scores in the CIWA-Ar scale than those with I/I allele. CONCLUSION: With current results, we suggested that ADH1B*2 and D allele of NQO2 may have a possible association with alcohol withdrawal symptoms and that they may play a protective role in the onset of alcohol dependence.