Gender Differences in Alcohol Metabolizing Hepatic Enzyme Genotypes in Korean Patients with Alcohol Dependence / 신경정신의학

OBJECTIVES: There are a number of preceding epidemiological studies reporting gender differences in the genetic etiology of alcohol dependence. The author investigated gender difference in the frequencies of ADH2 and ALDH2 genoypes between the patients with alcohol dependence and normal control. METHODS: The subjects were 141 alcohol dependent patients (104 males, 37 females) and 138 normal control (79 males, 59 females). The frequencies of 1/1 and 1/2+2/2 (2+ afterward) genotypes for ADH2 and ALDH2 were investigated in male and female between alcohol dependence and normal control group. DNA was extracted from WBC in peripheral venous blood and PCR-RFLP method was used out for genotyping. RESULTS: First, the frequency of ADH2 1/1 genotype was significantly higher in alcohol dependent patients than normal control in both genders. Second, while there was no gender difference in the frequency of ADH2 1/1 genotype in normal controls, in the patient group however, the frequency was significantly higher in females than males. Third, in male subjects with alcohol dependence, the frequency of ALDH2 1/1 genotype was significantly higher than in male normal control subjects. On the other hand, in female subjects with alcohol dependence, the frequency of ALDH2 2+ genotype was significantly higher than in female normal control subjects. CONCLUSION: These results suggest that while the risk of alcohol dependence is predominantly affected by ALDH2 1/1 genotype in male, the female ADH2 1/1 genotype is mainly associated with the risk of alcohol dependence. This means that there are gender differences in the genetic etiology of alcohol dependence.

Effects of Genetic Polymorphisms of Ethanol-Metabolizing Enzymes on Alcohol Drinking Behaviors / 대한간학회지

BACKGROUND/AIMS: Genetic variations of ethanol-metabolizing enzymes can affect alcohol drinking behavior. The aims of this study were to investigate and compare the distributions of these genetic polymorphisms between a healthy control group and a heavy drinker group which included an alcoholic liver cirrhosis group. METHODS: Genotypes of ADH2, ALDH2, CYP2E1, and catalase were identified by polymerase chain reaction and restriction fragment length polymorphism. Genomic DNA was extracted from peripheral leukocytes in 42 healthy controls, 12 heavy drinkers, and 30 alcoholic liver cirrhosis patients. RESULTS: 1) The genotype frequencies of ALDH2 (1*1), ADH2 (1*1), CYP2E1 (c1c1), and catalase1 (TT) were 69%, 55%, 38%, and 12%, respectively in healthy Korean males. 2) There was a significant difference in the distribution of the genetic polymorphism of ALDH2 between the control group and heavy drinker group (12 heavy drinkers and 30 alcoholic liver cirrhosis patients). The genotype frequency of ALDH2 mutant, ALDH2 (1*2) and ALDH2 (2*2) in the heavy drinker group (12%) was significantly lower than that in the control group (30%). 3) We didn't find anyone with ALDH2 homozygote mutant (DD) in the heavy drinker group. 4) There was no significant difference in the distribution of genetic polymorphisms in ADH2, CYP2E1 and catalase1 between the two groups. CONCLUSIONS: These results suggest that the absence of ALDH2 mutant genotype is strongly related to heavy drinking behavior. We can not prove, however, any evidence that the polymorphisms of other ethanol-metabolizing enzymes are associated with the determination of alcohol-drinking behavior.

Construction of Saccharomyces cerevisiae Mutant Deficient in adh2 and ald6 Genes / 微生物学通报

The purpose of this investigation is to improve ethanol production and decrease acetate formation in Saccharomyces cerevisiae strain YS2-?adh2.The strain YS2-?adh2 with deleted alcohol dehydrogenase Ⅱ(adh2) gene was isolated in our lab with higher ethanol production than that of the strain YS2.The ace-taldehyde dehydrogenase Ⅵ(ald6) gene encoded a cytosolic acetaldehyde dehydrogenase,a key enzyme of the pyruvate dehydrogenase(PDH) bypass,transfers acetaldehyde to acetate.To disrupt ald6 gene of the strain YS2-?adh2,ald6 gene targeting cassettes were synthesized by long flanking homology PCR(LFH-PCR) and then were transformed into YS2-?adh2 mutants by LiAc/SS Carrier DNA/PEG method.Positive transformants were selected with G418 and further confirmed by PCR.Once correctly integrated into the genome,the selective marker was rescued by transforming the plasmid pSH65 into the positive transformants and inducing the Cre expression with a Cre/loxP-mediated marker removal procedure.We named the ald6 gene knocked-out strain as YS2-?adh2-?ald6 which has a 12.5% higher ethanol production and a 18% lower acetate formation compared to the strain YS2.