Document Detail


Pharmacogenomics of maternal tobacco use: metabolic gene polymorphisms and risk of adverse pregnancy outcomes.
MedLine Citation:
PMID:  20177288     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To assess whether functional maternal or fetal genotypes along well-characterized metabolic pathways (ie, CYP1A1, GSTT1, and CYP2A6) may account for varying associations with adverse outcomes among pregnant women who smoke.
METHODS: DNA samples from 502 smokers and their conceptuses, alongside women in a control group, were genotyped for known functional allelic variants of CYP1A1 (Ile462Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys160His T>A). Modification of the association between smoking and outcome by genotype was evaluated. Outcomes included birth weight, pregnancy loss, preterm birth, small for gestational age, and a composite outcome composed of the latter four components plus abruption.
RESULTS: No interaction between maternal or fetal genotype of any of the polymorphisms and smoking could be demonstrated. In contrast, the association of smoking with gestational age-adjusted birth weight (birth weight ratio) was modified by fetal GSTT1 genotype (P for interaction=.02). Fetuses with GSTT1(del) had a mean birth weight reduction among smokers of 262 g (P=.01), whereas in fetuses without the GSTT1(del) the effect of tobacco exposure was nonsignificant (mean reduction 87 g, P=.16). After adjusting for confounding, results were similar.
CONCLUSION: Fetal GSTT1 deletion significantly and specifically modifies the effect of smoking on gestational age-corrected birth weight.
Authors:
Kjersti Aagaard-Tillery; Catherine Y Spong; Elizabeth Thom; Baha Sibai; George Wendel; Katharine Wenstrom; Philip Samuels; Hyagriv Simhan; Yoram Sorokin; Menachem Miodovnik; Paul Meis; Mary J O'Sullivan; Deborah Conway; Ronald J Wapner;
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Obstetrics and gynecology     Volume:  115     ISSN:  1873-233X     ISO Abbreviation:  Obstet Gynecol     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-23     Completed Date:  2010-03-17     Revised Date:  2012-01-24    
Medline Journal Info:
Nlm Unique ID:  0401101     Medline TA:  Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  568-77     Citation Subset:  AIM; IM    
Affiliation:
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah, USA. aagaardt@bcm.tmc.edu
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MeSH Terms
Descriptor/Qualifier:
Aryl Hydrocarbon Hydroxylases / genetics
Case-Control Studies
Cytochrome P-450 CYP1A1 / genetics
Female
Fetal Growth Retardation / genetics*
Gene Deletion
Genotype
Glutathione Transferase / genetics*
Humans
Infant, Low Birth Weight*
Infant, Newborn
Polymorphism, Single Nucleotide*
Pregnancy
Pregnancy Complications / genetics*
Prospective Studies
Smoking / genetics*
Grant Support
ID/Acronym/Agency:
DP2 OD001500-01/OD/NIH HHS; L40 HD051105-05/HD/NICHD NIH HHS; U01-HD36801/HD/NICHD NIH HHS; U10-HD21410/HD/NICHD NIH HHS; U10-HD21414/HD/NICHD NIH HHS; U10-HD27860/HD/NICHD NIH HHS; U10-HD27861/HD/NICHD NIH HHS; U10-HD27869/HD/NICHD NIH HHS; U10-HD27905/HD/NICHD NIH HHS; U10-HD27915/HD/NICHD NIH HHS; U10-HD27917/HD/NICHD NIH HHS; U10-HD34116/HD/NICHD NIH HHS; U10-HD34122/HD/NICHD NIH HHS; U10-HD34136/HD/NICHD NIH HHS; U10-HD34208/HD/NICHD NIH HHS; U10-HD34210/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 1.14.14.1/coumarin 7-hydroxylase; EC 2.5.1.-/glutathione S-transferase T1; EC 2.5.1.18/Glutathione Transferase

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


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