• International Journal of Oral Biology
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• v.31 no.3
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• pp.107-112
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• 2006

Aldehyde dehydrogenase (ALDH) plays an important role in alcohol metabolism; ALDH is responsible for the oxidation of acetaldehyde generated during alcohol oxidation. ALDH is also known to oxidize various other endogenous and exogenous aldehydes. Cytochrome P-450 2E1 (CYP2E1), a liver microsomal enzyme, also metabolizes acetaldehyde and ethanol and can be induced by other inducers including acetone and ethanol. We examined single nucleotide polymorphisms (SNP) of ALDH and CYP2E1 genotypes in Korean. Restriction fragment length polymorphism (RFLP) method was used to determine ALDH and CYP2E1 SNP. Mutation in ALDH was 60% (heterozygote 46.7% and homozygote 13.3%) among 15 cases. CYP2E1 mutation was 52.7% (heterozygote 47.4% and homozygote 5.3%) among 19 cases.

• Nutrition Research and Practice
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• v.9 no.1
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• pp.79-86
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• 2015

BACKGROUND/OBJECTIVES: It is well-known that alcohol consumption is associated with stroke risk as well as with aldehyde dehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated with stroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specific associations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population. SUBJECTS/METHODS: We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and free of stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases of stroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selected a single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism of ALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baseline questionnaire. RESULTS: Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2 polymorphism increased stroke risk among men. The multivariate hazard ratio [95% confidence interval] of stroke was 2.02 [1.03-3.99] for the wild-type allele compared with the mutant alleles, but the association was attenuated after controlling for alcohol consumption. Combinations of the wild-type allele and other risk factors of stroke, such as old age, diabetes mellitus, and habitual snoring, synergistically increased the risk among men. Among women, however, the ALDH2 polymorphism was not associated with stroke risk. CONCLUSIONS: The prospective cohort study showed a significant association between a common ALDH2 polymorphism and stroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain more risk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiable risk factors of stroke.

• Journal of Preventive Medicine and Public Health
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• v.37 no.4
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• pp.321-328
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• 2004

Objectives : The purpose of this study was to investigate the effect of genetic polymorphism of cytochrome P450 2E1 (CYP2E1) and aldehyde dehydrogenase 2 (ALDH2) on the xylene metabolism. Methods : Among 247 workers, 116 were occupationally exposed to xylene and 131 were not. Workers exposed to xylene had different work such as spray, touch-up, mix & assist, and pre-treat. Questionnaire variables were age, sex, use of personal protective equipment, smoking, previous night's drinking and work duration. The urinary methylhippuric acid was measured in the urine collected in the afternoon and corrected by urinary creatinine concentration. The genotypes of CYP2E1 and ALDH2 were investigated by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods with DNA extracted from venous blood. Results : 1. The urinary concentrations of o-, m-, and p-methylhippuric acid and total methylhippuric acid in the exposed group were significantly higher than those in the non-exposed group (p<0.001). 2. In multiple regression analysis, the urinary methylhippuric acid concentration was significantly influenced by exposure grade (Job-exposure matrixes), smoking, drug use and kind of protective equipment (p<0.1). 3. Genetic polymorphism of CYP2E1 and ALDH2 did not affect urinary methylhippuric acid level in the exposed group (p>0.05). Conclusions : Exposure grade, smoking, drug use and kind of protective equipment affected urinary methylhippuric acid level, whereas genetic polymorphism of CYP2E1 and ALDH2 did not. However, further investigation for the effect of genetic polymorphism on the metabolism of xylene with a larger sample size is needed.

• 대한예방의학회:학술대회논문집
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• 1996.10a
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• pp.419-420
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• 1996

• Korean Journal of Biological Psychiatry
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• v.17 no.1
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• pp.26-36
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• 2010

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 SNaPshot$^{TM}$ 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.

• 대한예방의학회:학술대회논문집
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• 1995.10a
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• pp.259-260
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• 1995

• Korean Journal of Biological Psychiatry
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• v.12 no.2
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• pp.196-206
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• 2005

Objectives:The purpose of this study is to evaluate the pathophysiology of alcoholics by investigating the differences in frequency of Aldehyde Dehydrogenase 2(ALDH2) genotypes and ALDH2 alleles between patients with alcohol dependence and controls, and the differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances. Methods:The authors selected 98 patients with alcohol dependence and 53 controls. Self-report questionnaires for acute reponses after alcohol ingestion, the AUI(Alcohol Use Inventory), and the NEO-PI-R(NEO Personality Inventory Revised) were given to all patients with alcohol dependence. ALDH2 genotypes were typed with MboII RFLP(Restriction Fragment Length Polymorphism) method in 53 controls and 98 patients with alcohol dependence. The authors divided alcoholic patients into two groups according to the presence of variant $ALDH2^2$ allele;normal ALDH2 alcoholics(N=87) and variant ALDH2 alcoholics(N=11). Results:1) The genotypic frequencies of subjects with $ALDH2^{1/1}$ were higher and those with $ALDH2^{1/2}$ and $ALDH2^{2/2}$ were lower in patients than in controls. 2) Alcohol dependence could be found in $ALDH2^{2/2}$ homozygote individuals. 3) Variant ALDH2 alcoholics had more family problems in the AUI than normal ALDH2 alcoholics. 4) Variant ALDH2 alcoholics experienced more flushing and cardiovascular responses after alcohol ingestion than normal ALDH2 alcoholics. 5) Variant ALDH2 alcoholics had less altruistic personality traits in the NEO-PI-R than normal ALDH2 alcoholics. 6) Variant ALDH2 alcoholics tended to have more tolerance to alcohol than normal ALDH2 alcoholics. Conclusion:Variant $ALDH2^2$ allele might play a protective role in the pathogenesis of alcohol dependence and there were several significant differences of drinking and personality traits in Korean male alcoholics with ALDH2 genotype variances.

• Korean Circulation Journal
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• v.52 no.3
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• pp.220-230
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• 2022

Background and Objectives: Previous observational studies presented a positive association between alcohol and atrial fibrillation (AF). However, previous studies using genetic polymorphisms on the causal relationship between alcohol consumption and AF have reported conflicting results. This study aimed to evaluate the causality between alcohol consumption and AF using the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which is the genetic variant with the most potent effect on drinking behavior. Methods: A total of 8,964 participants from the Dong-gu Study were included in the present study. The causal association between alcohol consumption and AF was evaluated through a Mendelian randomization (MR) analysis using the ALDH2 rs671 polymorphism as an instrumental variable. Results: No significant relationship between alcohol consumption and AF was found in the observational analysis. However, the genetic analysis using the ALDH2 polymorphism showed a significant association in men. In the MR analysis, genetically predicted daily alcohol consumption was positively related to AF. Conclusions: MR analysis revealed a significant association between the amount of alcohol consumption and AF, which suggests that the association may be causal.

• Korean Journal of Biological Psychiatry
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• v.9 no.1
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• pp.42-49
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• 2002

Objective:This study was to explore the relation of genetic polymorphisms of ALDH2 and CYP2E1 to clinical characteristics of alcoholic patients and alcohol induced liver damage. Methods:The genotype and allele frequencies of 128 male hospitalized patients who met DSM-IV criteria for alcohol dependence were compared with 128 healthy male control subjects. The genetic informations of ALDH2 and CYP2E1 were identified with the technique of polymerase chain reaction and restriction fragment length polymorphism. The clinical characteristics of the alcoholic patients were assessed and analyzed in relation to the family history of alcoholism. For the relation of CYP2E1 genetic polymorphism to the liver damage, the blood levels of various liver function indicators such as ALT, AST, and protein were checked out. Results:1) The alcoholic patients with the family history of alcoholism had the earlier onset of age (p=0.001), the longer duration of illness(p=0.045), and higher NCA scores(p=0.018) than those without the family history of alcoholism. 2) Most alcoholic patients were homozygous for $ALDH2^*1$, compared to control subjects.(p=0.000) 3) There was no difference of CYP2E1 distribution between alcoholic patients and control subjects. However, alcoholic patients having mutant c2 allele showed higher alcoholism severity scores(p=0.004) and more hospitalizations(p=0.014) than those having c1 allele. 4) There was no relationship between CYP2E1 genotype and the functional abnormalities of the liver. Conclusion:This study suggests that $ALDH2^*1$ is highly related with alcohol dependence. Also mutant c2 allele of CYP2E1 is correlated with the severity of alcoholism and the number of hospitalization. But genetic polymorphim of CYP2E1 seems to have no relation to liver damages.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.131-138
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• 2001

Objectives: Alcohol intake has been reported to be a risk factor of laryngeal cancer. Since the aldehyde dehydrogenase 2 (ALDH2) genotype is a major determinant of personal alcohol drinking habit, there is a possibility that ALDH2 genotype would be a risk factor for laryngeal cancer. N-Acetyltransferase 2 (NAT2) is a detoxifying enzyme and its polymorphism has been reported to be related to the risk of many environmental cancers. However, studies on the associations between these two genotypes and laryngeal cancer risk are scarce. We have assessed the effects of alcohol intake and the genotype of ALDH2 and NAT2 on the risk of laryngeal cancer in Koreans. Materials and Methods: Eighty-four pathologically proven laryngeal cancer patients and 168 age matched controls were included as the study subjects. Information about alcohol intake and smoking habit was collected using a self administered questionnaire. ALDH2 and NAT2 genotypes were analyzed using PCR-RFLP methods. Results: Alcohol intake was significant as a risk factor for laryngeal cancer (OR : 2.58, 95% CI : 1.24, 5.36), especially for supraglottic laryngeal cancer (OR : 3.24, 95% CI : 1.02, 10.31). Personal drinking habit was closely related with personal smoking habit, which was a potent risk factor of laryngeal cancer. In a stratified analysis according to the level of cumulative smoking amount, drinking was significant neither in light smokers (equal or less than 30 pack-years) nor in heavy smoker (over 30 pack-years). The ALDH2 genotype was significantly associated with the risk of laryngeal cancer in a univariate analysis. The statistical significance, however, disappeared after adjusting alcohol intake using a multiple conditional logistic model. The NAT2 genotype was not significant as a risk factor for laryngeal cancer. Conclusion: Alcohol drinking and ALDH2 genotype would have indirect effects on laryngeal cancer by their correlations with cigarette smoking or with alcohol drinking. It is less likely that the NAT2 genotype would be a potent risk factor of laryngeal cancer.