Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
11584143
TITLE
Variation in alcohol pharmacokinetics as a risk factor for alcohol dependence.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
The significant association between alcohol dehydrogenase (ADH)-2 genotype and alcohol-dependence risk, demonstrated in both Asian and non-Asian populations, suggests a link between the metabolism of alcohol (ethanol) and individual differences in susceptibility to dependence.
METHODS NlmCategory: METHODS
We tested this hypothesis by following up on subjects who took part in the Alcohol Challenge Twin Study conducted in 1979-1981 and comparing the blood and breath alcohol results in that study between subjects who subsequently did or did not meet diagnostic criteria for lifetime alcohol dependence in 1992-1993.
RESULTS NlmCategory: RESULTS
Subjects who met DSM-III-R criteria for lifetime alcohol dependence at follow-up had higher blood and breath alcohol values after alcohol challenge than never-dependent subjects. Multivariate analysis showed independent effects of susceptibility to alcohol dependence and smoking status on blood alcohol concentrations, whereas habitual alcohol intake at the time of the initial study had marginally significant effects. The risk of alcohol dependence was 2-fold higher in men and 3-fold higher in women with blood or breath alcohol concentrations in the highest quartile than in the lowest quartile.
CONCLUSIONS NlmCategory: CONCLUSIONS
In view of this association and the known genetic influences on both alcohol pharmacokinetics and alcohol dependence, it is probable that part of the heritability of dependence is mediated by genes (other than the known ADH2 and ADH3 polymorphisms) affecting alcohol metabolism.
DATE PUBLISHED
2001 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2001/10/05 10:00
medline 2001/10/26 10:01
entrez 2001/10/05 10:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Whitfield JB Whitfield J B JB Department of Clinical Biochemistry, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia. johnwhit@bioc.rpa.cs.nsw.gov.au
Zhu G Zhu G G
Duffy DL Duffy D L DL
Birley AJ Birley A J AJ
Madden PA Madden P A PA
Heath AC Heath A C AC
Martin NG Martin N G NG
INVESTIGATORS
JOURNAL
VOLUME: 25
ISSUE: 9
TITLE: Alcoholism, clinical and experimental research
ISOABBREVIATION: Alcohol. Clin. Exp. Res.
YEAR: 2001
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0145-6008
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Alcohol Clin Exp Res
COUNTRY: England
ISSNLINKING: 0145-6008
NLMUNIQUEID: 7707242
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10249 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Alcohol Dehydrogenase genetics
Alcoholism metabolism
Breath Tests metabolism
Ethanol pharmacokinetics
Female pharmacokinetics
Genetic Predisposition to Disease pharmacokinetics
Genotype pharmacokinetics
Humans pharmacokinetics
Isoenzymes genetics
Male genetics
Risk Factors genetics
Smoking genetics
Twins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Isoenzymes
3K9958V90M Ethanol
EC 1.1.1.1 Alcohol Dehydrogenase
OTHER ID's