title: Pharmacogenomics of maternal tobacco use: metabolic gene polymorphisms and risk of adverse pregnancy outcomes.
abstract: 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.
  
  
  CONCLUSIONS
  Fetal GSTT1 deletion significantly and specifically modifies the effect of smoking on gestational age-corrected birth weight.
authors.affiliation: From the Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah; University of Tennessee, Memphis, Tennessee; University of Texas Southwestern Medical Center, Dallas, Texas; University of Alabama at Birmingham, Birmingham, Alabama; The Ohio State University, Columbus, Ohio; University of Pittsburgh, Pennsylvania; Wayne State University, Detroit, Michigan; University of Cincinnati, Cincinnati, Ohio; Wake Forest University Health Services, Winston-Salem, North Carolina; University of Miami, Miami, Florida; University of Texas at San Antonio, San Antonio, Texas; Thomas Jefferson University, Philadelphia, Pennsylvania; The George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute for Child Health and Human Development, Bethesda, Maryland.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Aagaard-Tillery
authors.forename: Catherine Y
authors.initials: CY
authors.lastname: Spong
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thom
authors.forename: Baha
authors.initials: B
authors.lastname: Sibai
authors.forename: George
authors.initials: G
authors.lastname: Wendel
authors.forename: Katharine
authors.initials: K
authors.lastname: Wenstrom
authors.forename: Philip
authors.initials: P
authors.lastname: Samuels
authors.forename: Hyagriv
authors.initials: H
authors.lastname: Simhan
authors.forename: Yoram
authors.initials: Y
authors.lastname: Sorokin
authors.forename: Menachem
authors.initials: M
authors.lastname: Miodovnik
authors.forename: Paul
authors.initials: P
authors.lastname: Meis
authors.forename: Mary J
authors.initials: MJ
authors.lastname: O'Sullivan
authors.forename: Deborah
authors.initials: D
authors.lastname: Conway
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wapner
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D017353:Gene Deletion; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics*; D011446:Prospective Studies; D012907:Smoking / Q000235:genetics*
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D019363:Cytochrome P-450 CYP1A1; D065637:Cytochrome P-450 CYP2A6; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase