Adverse Birth Outcomes Associated with Maternal Smoking and Polymorphisms in the N-Nitrosamine-Metabolizing Enzyme Genes NQO1 and CYP2E1

• Published in: American journal of epidemiology Vol. 167; no. 6; pp. 719 - 726
• Main Authors: Sasaki, Seiko, Sata, Fumihiro, Katoh, Shizue, Saijo, Yasuaki, Nakajima, Sonomi, Washino, Noriaki, Konishi, Kanae, Ban, Susumu, Ishizuka, Mayumi, Kishi, Reiko
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 15.03.2008; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Analysis. Health state; Asian people; Biological and medical sciences; Birth weight; cytochrome P-450 CYP2E1; Enzymes; Epidemiology; Female; fetal development; Fetuses; General aspects; Genetic Predisposition to Disease; Genotypes; human; Humans; Infant Welfare; Infant, Low Birth Weight; Infant, Newborn; Infants; Japan; Linear Models; Maternal Welfare; Medical sciences; NAD(P)H Dehydrogenase (Quinone) - genetics; nitrosamines; Nitrosamines - metabolism; NQO1 protein; Polymorphism; Polymorphism, Genetic; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal development; Prospective Studies; Proteins; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk Factors; Risk-Taking; Side effects; Smoking; Tobacco Smoke Pollution - adverse effects; Tobacco, tobacco smoking; Toxicology; Japan; Sapporo Japan; Japan, Hokkaido, Sapporo; birth weight; nitrosamines; pregnancy; smoking; NQO1 protein, human; pregnancy outcome; cytochrome P-450; fetal development; Human; birth weight; cytochrome P-450 CYP2E1; fetal development; nitrosamines; NQO1 protein; Enzyme; Cytochrome P450; Nitrosamine; Tobacco smoking; Birth; human; pregnancy; pregnancy outcome; smoking; Pregnancy; Fetal development; Tobacco; Mother; Complication; Female; Birth weight; Woman; Public health; Polymorphism
• ISSN: 0002-9262; 1476-6256; 1476-6256
• DOI: 10.1093/aje/kwm360

Maternal smoking during pregnancy can result in both pregnancy complications and reduced size of the fetus and neonate. Among women who smoke, genetic susceptibility to tobacco smoke also is a likely causative factor in adverse pregnancy outcomes. A prospective cohort study was conducted among 460 pregnant women who delivered live singletons in Sapporo, Japan, from 2002 to 2005. Multiple linear regression models were used to estimate associations of maternal smoking and polymorphisms in two genes encoding N-nitrosamine-metabolizing enzymes—NAD(P)H: quinone oxidoreductase 1 (NQO1) and cytochrome P-450 2E1 (CYP2E1)—with birth size. Among infants born to smokers with the NQO1 homozygous wild-type allele, birth weight, birth length, and birth head circumference were significantly reduced (p < 0.01 for each factor). For the homozygous wild-type CYP2E1 allele, birth weight was lower by an estimated 195 g (standard error, 55; p < 0.001) among smokers. These genotypes did not confer adverse effects among women who had never smoked or who quit smoking during the first trimester. The adverse effects of maternal smoking on infant birth size may be modified by maternal genetic polymorphisms in N-nitrosamine-metabolizing enzymes among Japanese subjects. These results may help in directing smoking cessation interventions during pregnancy, especially among susceptible women.