TY - JOUR
T1 - Pharmacogenomics of maternal tobacco use
T2 - Metabolic gene polymorphisms and risk of adverse pregnancy outcomes
AU - Aagaard-Tillery, Kjersti
AU - Spong, Catherine Y.
AU - Thom, Elizabeth
AU - Sibai, Baha
AU - Wendel, George
AU - Wenstrom, Katharine
AU - Samuels, Philip
AU - Simhan, Hyagriv
AU - Sorokin, Yoram
AU - Miodovnik, Menachem
AU - Meis, Paul
AU - O'Sullivan, Mary J.
AU - Conway, Deborah
AU - Wapner, Ronald J.
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
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U2 - 10.1097/AOG.0b013e3181d06faf
DO - 10.1097/AOG.0b013e3181d06faf
M3 - Article
C2 - 20177288
AN - SCOPUS:77649113593
SN - 0029-7844
VL - 115
SP - 568
EP - 577
JO - Obstetrics and gynecology
JF - Obstetrics and gynecology
IS - 3
ER -