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±431mL, forced expiratory volume in the first 1s (FEV ₁)=1440 ±360mL, percent FEV ₁/FVC ratio=89±12, and forced expiratory flow between the 25% and 75% of FVC (FEF _25-75)=1745±603mL. In addition to a tobacco effect on FVC (-131mL, 95% CI: -245, -17) and FEV ₁/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 -734mL (95% CI: -1206, -262) reductions in FEV ₁ and -825mL (95% CI: -909, -795) reductions in FVC; reduced smoking was still associated with -590mL (95% CI: -629, -551) reductions in FVC. For children of mothers with GSTM1 deletion, persistent daily smoking was associated with -176mL (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.