Alcohol sensitivity related to polymorphism of alcohol-metabolizing enzymes in Japanese

Mizoi, Y; Tatsuno, Yoshitsugu; Adachi, Junko; Kogame, M; Fukunaga, Tetsuo; Fujiwara, Satoshi; Hishida, Shigeru; Ijiri, Iwao

doi:10.1016/0091-3057(83)90159-4

Cited by 160 publications

(80 citation statements)

References 8 publications

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“…Of note, significant debate exists about the ubiquity of acetaldehyde's aversiveness, with some studies suggesting that brain-derived acetaldehyde may actually partially mediate alcohol's rewarding effects (Israel et al, 2013;Ledesma & Aragon, 2013;Rodd et al, 2005), whereas peripheral acetaldehyde causes the aversive physiological effects (Israel et al, 2013;Mizoi et al, 1983;Shimoda et al, 1996). Although speculative at this point and in need of direct empirical examination in future studies with large samples, the results of this study are consistent with the possibility that brain acetaldehyde may actually be reinforcing.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Environmental Predictors of Alcohol Use in Asian American Young Adults

Bujarski

Lau

Lee

et al. 2015

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Among Asian American young adults, variations in alcohol-metabolizing genes (i.e., aldehyde dehydrogenase [ALDH2] and alcohol dehydrogenase [ADH1B]) are protective, whereas Korean ethnicity, family history of alcohol problems (FH), and acculturation represent risk factors for alcohol misuse. This study aims to integrate these genetic and environmental factors in a sample of Asian Americans expressing a wide range of alcohol use behaviors and problems. Method: Participants were 97 Asian American young adults (42% female) recruited as heavy and light drinkers (n = 49 and 48, respectively). Participants completed the Alcohol Use Disorders Identification Test, Timeline Followback, Vancouver Acculturation Index, and Family Tree Questionnaire. All participants provided buccal cell samples for DNA analysis. Results: Family history-positive (FH+) subjects reported greater alcohol use than family history-negative (FH−) subjects. A FH × ALDH2 interaction was observed such that FH− subjects demonstrated no ALDH2 effect, yet in FH+ subjects, the ALDH2*2 genotype was associated with increased alcohol use. A significant main effect of acculturation was also moderated by FH such that the positive association between acculturation and alcohol use was greater among FH+ subjects and, in particular, among FH+ men. Conclusions: Although preliminary, these results suggest that the potential protective effects conferred by ALDH2 and ADH1B are moderated by FH, such that a positive FH appeared to abolish the protective effect of these genes. Further, acculturation was associated with greater alcohol use in FH+ subjects only. If replicated in larger samples, these data suggest that alcohol-metabolism genes may not be protective in the context of high environmental risk. (J. Stud. Alcohol Drugs, 76, 690-699, 2015)

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Section: Discussionmentioning

confidence: 99%

Genetic and Environmental Predictors of Alcohol Use in Asian American Young Adults

Bujarski

Lau

Lee

et al. 2015

J. Stud. Alcohol Drugs

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“…The ALDH2 *2 allele is linked to alcohol-related flushing, an adverse reaction to the metabolism of alcohol that includes reddening of the face, headaches, nausea, drowsiness, and abnormal heart beats (4,5). Alcohol-related flushing occurs when a deficient enzyme, for metabolizing acetaldehyde, the primary metabolite of alcohol, to acetate, results in a buildup of acetaldehyde in the body (6). Studies show that individuals who carry ALDH2 *2 drink less frequently, consume smaller quantities of alcohol, and have a reduced risk for alcohol dependence (2,7,8).…”

Section: Introductionmentioning

confidence: 99%

*ALDH2**2 and peer drinking in East Asian college students

O'Shea

Thomas

Webb

et al. 2017

The American Journal of Drug and Alcohol Abuse

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Background: The ALDH2*2 allele (A-allele) at rs671 is more commonly carried by Asians and is associated with alcohol-related flushing, a strong adverse reaction to alcohol that is protective against drinking. Social factors, such as having friends who binge drink, also contribute to drinking in Asian youth. Objectives: This study examined the interplay between ALDH2*2, peer drinking, and alcohol consumption in college students. We hypothesized that the relationship between ALDH2*2 and standard grams of ethanol per month would vary based on the level of peer drinking. Methods: Subjects (N = 318, 63.25% female) were East Asian college students in the United States who reported drinking alcohol. Data were from the freshman year of a university survey that included a saliva DNA sample. ALDH2*2 status was coded ALDH2*2(+) (A/G and A/A genotypes) and ALDH2*2(−) (G/G genotype). Peer drinking was students’ perception of how many of their friends “got drunk”. Results: Main effects of ALDH2*2(−) and having more friends who got drunk were associated with greater alcohol consumption. The ALDH2*2 × peer drunkenness interaction showed a stronger positive association with alcohol consumption for ALDH2*2(−) versus ALDH2*2(+) at increasing levels of peer drunkenness. Follow-up comparisons within each peer drunkenness level identified significantly higher alcohol consumption for ALDH2*2(−) compared to ALDH2*2(+) at the all friends got drunk level.Conclusion: There was evidence of a stronger effect for ALDH2*2(−) compared to ALDH2*2(+) with greater alcohol use when students were more exposed to peer drinking. Findings contribute to a growing literature on the interrelationships between genetic influences and more permissive environments for alcohol consumption.

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“…0.1 mM 1 h after drinking, while it was 0.001 mM for controls. 29) For the formation of the CPrGua adduct, two molecules of AA are needed and dilution of AA can be greatly disadvantageous from the viewpoint of kinetics of the reaction. Experimentation under the conditions of lower concentration of AA is in progress, to obtain information reflecting a more practical situation in human tissues.…”

Section: Semi-micro Hplc Separations and Ms Detection Of Nucleobasesmentioning

confidence: 99%

LC-MS Study on the Formation of Cyclic 1,N2-Propano Guanine Adduct in the Reactions of DNA with Acetaldehyde in the Presence of Histone

Inagaki

Esaka

Goto

et al. 2004

Biological & Pharmaceutical Bulletin

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Acetaldehyde (AA) and crotonaldehyde (CA, 2-butenal in IUPAC nomenclature) are reactive, ubiquitous aldehydes, which are present in the environment, and the strong carcinogenic property of CA has been confirmed and the carcinogenicity of AA has been strongly suspected. 1-7)CA reacts with the exocyclic amino group of guanine in DNA to form cyclic 1,N 2 -propano guanine (CPr-Gua) adduct as a main DNA adduct. 8,9) The structure of CPr-Gua is shown in Fig. 1. The exogenous exposure of humans to CA can occur by inhalation of cigarette smoke or automobile exhaust gases. A substantial amount of the CPr-Gua adducts has also detected in oral tissue DNA, with increased amounts in cigarette smokers.10) On the other hand, using a highly sensitive 32 P-postlabeling method, CPr-Gua has been detected in a variety of tissues of untreated rats and mice and in human liver, mammary glands and leukocytes, and this will be in part ascribed to CA arising from endogeneous lipid peroxidation.11-13) Thus, the "CA-derived" CPr-Gua adducts will have both exogenous and endogeneous sources.The main source of exposure to AA for the majority of the general population is through the metabolism of alcohol from drinks. It is formed endogenously as a primary product during the metabolic oxidation of ethanol by alcohol dehydrogenases in the liver. The N 2 -ethylguanine (Et-Gua, see Fig. 1) adduct was detected in granulocyte and lymphocyte DNA of alcoholic patients and this adduct has been considered to be a major DNA adduct by AA. [14][15][16][17][18][19] There is a possibility that Et-Gua would induce G-C transversion in vivo. 18,19) On the other hand, recently, the CPr-Gua adduct also has been considered to be another major DNA adduct of AA. [20][21][22] This adduct is considered to cause either base substitution or frameshift mutations.11) Wang et al. reported that the CPr-Gua adduct was formed in reactions of 2Ј-deoxyguanosine (dG) or calf thymus DNA with AA. 20) In our previous work, formation of the CPr-Gua adducts was observed in DNA of cultured HL-60 cells exposed to AA. 22)Wang et al. suggested that there are two path ways to the CPr-Gua adduct, namely, that from CA formed by the aldol condensation of AA and that from consecutive reaction of two molecules of AA. 20) One of the co-authors (M.S.) has reported that the reactions of guanine nucleosides and nucleotides with AA are significantly accelerated under mild conditions by addition of some basic amino acids such as arginine and lysine to give the corresponding cyclic 1,N 2 -propano derivatives almost quantitatively.21) Both aldol condensation of AA to CA and the formation of the CPr-Gua adduct from CA would be accelerated strongly by the added basic amino acids.Is there any biological meaning to this remarkable acceleration by the basic amino acids?-This is a question which is the major subject of this work. We hypothesized that the basic amino acids may be those in histone. Histone is essential for DNA packaging and contains a large amount of basic amino acids such as arginine and lys...

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Alcohol sensitivity related to polymorphism of alcohol-metabolizing enzymes in Japanese

Cited by 160 publications

References 8 publications

Genetic and Environmental Predictors of Alcohol Use in Asian American Young Adults

Genetic and Environmental Predictors of Alcohol Use in Asian American Young Adults

*ALDH2**2 and peer drinking in East Asian college students

LC-MS Study on the Formation of Cyclic 1,N2-Propano Guanine Adduct in the Reactions of DNA with Acetaldehyde in the Presence of Histone

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Alcohol sensitivity related to polymorphism of alcohol-metabolizing enzymes in Japanese

Cited by 160 publications

References 8 publications

Genetic and Environmental Predictors of Alcohol Use in Asian American Young Adults

Genetic and Environmental Predictors of Alcohol Use in Asian American Young Adults

ALDH2*2 and peer drinking in East Asian college students

LC-MS Study on the Formation of Cyclic 1,N2-Propano Guanine Adduct in the Reactions of DNA with Acetaldehyde in the Presence of Histone

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*ALDH2**2 and peer drinking in East Asian college students