Combinations of CYP2A6*4 and glutathione S-transferases gene polymorphisms modify the association between maternal secondhand smoke exposure during pregnancy and small-for-gestational-age

Introduction: Risk of small-for-gestational-age (SGA) birth varied considerably in women exposed to secondhand smoke (SHS) during pregnancy. We examined whether this variation was explained by mothers' one Phase I (CYP2A6*4, activation of tobacco toxics) and two Phase II (GSTM1 and GSTT1, detoxification) metabolic genotypes. Methods: We enrolled 468 Chinese pregnant women (115 delivering SGA and 353 delivering non-SGA newborns) shortly before delivery. SHS exposure during pregnancy was defined as selfreported daily exposure time being more than 0 minute. We fitted multivariable logistic regression models to examine whether CYP2A6*4, GSTM1, and GSTT1 gene polymorphsims and their combinations modified the association between SHS exposure and SGA. Results: In the total sample, more mothers of SGA newborns were exposed to SHS during pregnancy than mothers of non-SGA newborns (38.3% vs. 31.4%). CYP2A6*4, GSTM1, and GSTT1 genes alone could not modify the association between SHS exposure and SGA. The combination of CYP2A6*4 and GSTT1 high-risk genotypes (CYP2A6*1/*1 and GSTT1-absent [high-risk] vs. other combinations as a whole [low-risk]) significantly (P value, .045) modified the association between SHS exposure and SGA. Among mothers with high-risk genotypes, SHS during pregnancy was significantly associated with SGA (confounder-adjusted odds ratio, 2.31 [95% confidence interval, 1.20-4.42]). Among mothers with low-risk genotypes, however, SHS exposure during pregnancy was not associated with SGA (1.14 [0.64-2.04]). Conclusions: Chinese pregnant women with the combination of CYP2A6*1/*1 and GSTT1-absent genotypes are at particularly high-risk of SHS-related SGA.