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

Nicotine Tob Res. 2015 Dec;17(12):1421-7. doi: 10.1093/ntr/ntv072. Epub 2015 Apr 6.

Abstract

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 self-reported 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics
  • Case-Control Studies
  • Cytochrome P-450 CYP2A6 / genetics*
  • Female
  • Genetic Association Studies / methods
  • Glutathione Transferase / genetics*
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age / physiology*
  • Polymorphism, Genetic / genetics
  • Pregnancy
  • Prenatal Exposure Delayed Effects / diagnosis
  • Prenatal Exposure Delayed Effects / enzymology
  • Prenatal Exposure Delayed Effects / genetics*
  • Smoking / adverse effects
  • Smoking / genetics*
  • Tobacco Smoke Pollution / adverse effects*

Substances

  • Tobacco Smoke Pollution
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1