Document Detail


Alcohol dehydrogenase-2*3 allele protects against alcohol-related birth defects among African Americans.
MedLine Citation:
PMID:  9399981     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Considerable variation in offspring outcome is observed after intrauterine alcohol exposure. The underlying mechanism may include genetic diversity in the enzymes responsible for alcohol metabolism. Of the known genetic polymorphisms, differences at the alcohol dehydrogenase-2 locus (ADH2) are likely most critical because the resulting enzymes are >30-fold different in their kinetic constants. To test whether differences in maternal or offspring ADH2 genotype are determinants of risk for alcohol-related birth defects, maternal-infant pairs (n = 243) were enrolled on the basis of maternal alcohol intake during pregnancy and maternal ADH2 genotype. Infant outcome was measured using the Bayley Scales of Infant Development Mental Index (MDI) at 12 months of age. Drinking during pregnancy was associated with lower MDI scores but only in the offspring of mothers without an ADH2*3 allele (P < .01, analysis of variance, post hoc). The offspring of drinking women with at least one ADH2*3 allele had MDI scores similar to those of nondrinking women of either ADH2 genotype. Lower MDI scores were associated with the three-way interaction among increasing alcohol intake and maternal and offspring absence of the ADH2*3 allele (P < .01, multiple linear regression). We suggest that the protection afforded by this allele is secondary to its encoding of the high-Km/high-Vmax ADH beta3 isoenzyme, which would provide more efficient alcohol metabolism at high blood alcohol concentrations. These observations are supportive of alcohol, rather than acetaldehyde, being the more important proximate teratogen and are the first observations of a specific genetic explanation for susceptibility differences to alcohol-related birth defects.
Authors:
D G McCarver; H R Thomasson; S S Martier; R J Sokol; T Li
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  283     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-01-15     Completed Date:  1998-01-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1095-101     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USA.
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Drug-Induced / ethnology,  genetics*,  prevention & control
Adolescent
Adult
African Continental Ancestry Group / genetics*
Alcohol Dehydrogenase / genetics*
Alleles*
Female
Genotype
Growth
Humans
Infant, Newborn
Isoenzymes / genetics*
Male
Pregnancy
Grant Support
ID/Acronym/Agency:
AA07606/AA/NIAAA NIH HHS; AA07611/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Isoenzymes; EC 1.1.1.1/Alcohol Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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