母体烟草使用的药物基因组学：代谢基因多态性与不良妊娠结局的风险。
Pharmacogenomics of maternal tobacco use: metabolic gene polymorphisms and risk of adverse pregnancy outcomes.
机构信息
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.
出版信息
Obstet Gynecol. 2010 Mar;115(3):568-577. doi: 10.1097/AOG.0b013e3181d06faf.
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.
目的
评估功能型母体或胎儿基因型是否可以解释在吸烟孕妇中，其代谢途径（即 CYP1A1、GSTT1 和 CYP2A6）的特征良好，而与不良结局的关联则存在差异。
方法
对 502 名吸烟者及其胚胎以及对照组中的女性的 DNA 样本进行了 CYP1A1（Ile462Val AA>AG/GG）、GSTT1（缺失）和 CYP2A6（Lys160His T>A）已知功能等位基因变异的基因分型。评估了基因型对吸烟与结局之间关联的修饰作用。结局包括出生体重、妊娠丢失、早产、小于胎龄儿和由后四种成分加胎盘早剥组成的复合结局。
结果
没有发现任何多态性的母体或胎儿基因型与吸烟之间存在交互作用。相比之下，吸烟与胎龄校正出生体重（出生体重比）的关联受到胎儿 GSTT1 基因型的修饰（交互作用 P 值为.02）。携带 GSTT1（缺失）的胎儿在吸烟者中的平均出生体重下降了 262 克（P=.01），而在没有 GSTT1（缺失）的胎儿中，烟草暴露的影响无统计学意义（平均减少 87 克，P=.16）。调整混杂因素后，结果相似。
结论
胎儿 GSTT1 缺失显著且特异性地修饰了吸烟对胎龄校正出生体重的影响。
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