Fetal Genotype for the Xenobiotic Metabolizing Enzyme NQO1 Influences Intrauterine Growth Among Infants Whose Mothers Smoked During Pregnancy


  • The authors thank Kathakali Addya for supervising the genotyping, Madhavi Vaddi for performing the genotyping assays, Charles Curtis for a great deal of technical laboratory assistance, Andy McMillan for data management, and Steve Whitehead for inspiration and encouragement. This work was supported by grants from the Merck Foundation (to S.R.J.) and from the American Heart Association (National Scientist Development Grant 0430148N to T.G.).

concerning this article should be addressed to Thomas S. Price, P080 SGDP Centre, Institute of Psychiatry, Kings College London, London SE5 8AF, UK. Electronic mail may be sent to thomas.price@kcl.ac.uk.


Maternal smoking during pregnancy retards fetal growth and depresses infant birth weight. The magnitude of these effects may be moderated by fetal genotype. The current study investigated maternal smoking, fetal genotype, and fetal growth in a large population sample of dizygotic twins. Maternal smoking retarded fetal growth in a dose-dependent fashion. In a subsample of 497 twin pairs whose mothers smoked during pregnancy, a functional polymorphism in the NAD(P)H:quinone oxidoreductase gene (NQO1 Pro187Ser; rs1800566) was significantly associated with fetal growth within families. The effect was strongest among moderate smokers. This is the first demonstration that fetal genotype for an enzyme involved in tobacco smoke metabolism influences intrauterine growth independent of maternal genotype. Future studies should conduct formal tests of Fetal Genotype × Maternal Smoking interactions.