Journal
OBSTETRICS AND GYNECOLOGY
Volume 115, Issue 3, Pages 568-577Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/AOG.0b013e3181d06faf
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Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10-HD27869, U10-HD21414, U01-HD36801, U10-HD34208, U10-HD27860, U10-HD34116, U10-HD34136, U10-HD27861, U10-HD34122, U10-HD21410, U10-HD27915, U10-HD34210, U10-HD27905, U10-HD27917]
- National Institutes of Health
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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 (Ile(462)Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys(160)His 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. (Obstet Gynecol 2010;115:568-77)
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