Maternal smoking during pregnancy, polymorphic CYP1A1 and GSTM1, and lung-function measures in urban family children

Purpose

Understanding the interplay between genes and in-utero tobacco exposure in affecting child lung development is of great significance. In this study, we tested the hypothesis that tobacco-related lung-function reduction in children differs by maternal polymorphic genes Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase Mu 1 (GSTM1).

Materials and methods

Data were collected among 370 children (6–10 years old, 81.6% African-Americans) and their biological mothers visiting a large children’s hospital. Study hypotheses were tested using multiple regression method.

Results

Among the study sample, 143 mothers smoked throughout pregnancy and 72 smoked on a daily basis. Spirometric measures (mean±SD) included were: forced vital capacity (FVC)=1635±431 mL, forced expiratory volume in the first 1 s (FEV₁)=1440 ±360 mL, percent FEV₁/FVC ratio=89±12, and forced expiratory flow between the 25% and 75% of FVC (FEF_25–75)=1745±603 mL. In addition to a tobacco effect on FVC (−131 mL, 95% CI: −245, −17) and FEV₁/FVC ratio (42, 95% CI: 1, 83), regression analysis controlling for covariates indicated that for the subsample of children whose mothers were CYP1A1?2A homozygous, maternal daily smoking was associated with −734 mL (95% CI: −1206, −262) reductions in FEV₁ and −825 mL (95% CI: −909, −795) reductions in FVC; reduced smoking was still associated with −590 mL (95% CI: −629, −551) reductions in FVC. For children of mothers with GSTM1 deletion, persistent daily smoking was associated with −176 mL (95% CI: −305, −47) reductions in FVC.

Discussion and conclusions

Maternal smoking during pregnancy was significantly associated with lung-function reduction in children, particularly for those whose mothers possessed the polymorphic CYP1A1*2A and GSTM1 deletion.