title: 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.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Biostatistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China;
authors.forename: Chuanbo
authors.initials: C
authors.lastname: Xie
authors.affiliation: Division of Behavioral Medicine, Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY;
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Biostatistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China;
authors.forename: Zhongzheng
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Biostatistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China;
authors.forename: Peng
authors.initials: P
authors.lastname: Ding
authors.affiliation: Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China;
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China;
authors.forename: Yanhui
authors.initials: Y
authors.lastname: He
authors.affiliation: Shenzhen Women and Children's Hospital, Shenzhen, China;
authors.forename: Jianmiao
authors.initials: J
authors.lastname: Lin
authors.affiliation: Shenzhen Women and Children's Hospital, Shenzhen, China;
authors.forename: Shixin
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Foshan Women and Children's Hospital, Foshan, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Guo
authors.affiliation: Foshan Women and Children's Hospital, Foshan, China.
authors.forename: Deqin
authors.initials: D
authors.lastname: Jia
authors.affiliation: Department of Biostatistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China; chenwq@mail.sysu.edu.cn.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Chen
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D065637:Cytochrome P-450 CYP2A6; D005982:Glutathione Transferase; D014028:Tobacco Smoke Pollution; C585710:CYP2A6 protein, human; C413545:glutathione S-transferase T1