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

Abstract

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.

Inhibitory effects of maternal smoking on the development of severe retinopathy of prematurity

“…10 They reported smoking an average of 13.0 (range: 2-30) cigarettes per day. Birth weight, duration of artificial ventilation including CPAP, total duration of oxygen supplementation, the presence of CLD, and maternal smoking were determined to be significantly different between the severe and non-severe ROP groups by univariate logistic regression analysis (Table 1).…”

“…The history of cigarette smoking was self-reported by each mother, and recorded in the maternal and infant medical records at the first visit to the mother and baby centre of Kobe University. 10 Women who did not smoke at any time during pregnancy were included in the group of non-smokers. Women who continued to smoke during pregnancy with any frequency were included in the group of smokers.…”

“…In addition, as the prevalence of maternal smoking is estimated at about 18-20% in Japanese society, investigating the effect of smoking on the development of ROP is an important issue. 10 In this study, we performed a statistical evaluation on clinical risk factors including maternal smoking for the incidence of severe ROP in the Japanese population.…”

A common FMO3 polymorphism may amplify the effect of nicotine exposure in sudden infant death syndrome (SIDS)

“…Several enzymes are involved in this metabolism, such as NAD(P)H: quinine oxidoreductase 1 (NQO1), cytochrome P-450 1A1 (CYP1A1), cytochrome P-450 2E1 (CYP2E1) or glutathione-S-transferases. Regarding NQO1 and CYP2E1, an association has been found between polymorphisms in these genes and birth weight or birth head circumference in infants born to smokers [13]. Variants in CYP1A1 and GSTT1 have been shown to alter the metabolic detoxification process for cigarette smoke [14], but no association between these genes and SIDS risk could be demonstrated [15].…”

Combined effects of AHR , CYP1A1 , and XRCC1 genotypes and prenatal maternal smoking on infant birth size: Biomarker assessment in the Hokkaido Study

“…Data were generated from these participants by means of baseline questionnaires, biochemical assays, birth records, and four-month 4-month postpartum questionnaires. To date, there have been only three reports on the association between prenatal smoking, maternal genetic polymorphisms, and infant birth size [8,12,38]. Figure 1 shows the flow diagram for the participants in this study.…”