title: Modification of the association between maternal smoke exposure and congenital heart defects by polymorphisms in glutathione S-transferase genes.
abstract: Congenital heart defects (CHDs) arise through various combinations of genetic and environmental factors. Our study explores how polymorphisms in the glutathione S-transferase (GST) genes affect the association between cigarette smoke exposure and CHDs. We analysed 299 mothers of children with CHDs and 284 mothers of children without any abnormalities who were recruited from six hospitals. The hair nicotine concentration (HNC) was used to quantify maternal smoke exposure, and the maternal GSTT1, and GSTM1 and GSTP1 genes were sequenced. We found a trend of higher adjusted odds ratios with higher maternal HNC levels, suggesting a dose-response relationship between maternal smoke exposure and CHDs. The lowest HNC range associated with an increased risk of CHDs was 0.213-0.319 ng/mg among the mothers with functional deletions of GSTM1 or GSTT1and 0.319-0.573 ng/mg among the mothers with normal copies of GSTM1 and GSTT1. In addition, the adjusted odds ratio for an HNC of >0.573 ng/mg was 38.53 among the mothers with the GSTP1 AG or GG genotype, which was 7.76 (χ(2) = 6.702, p = 0.010) times greater than the AOR in the mothers with GSTP1 AA genotype. Our study suggests that polymorphisms of maternal GST genes may modify the association of maternal smoke exposure with CHDs.
authors.affiliation: National Center for Birth Defect Monitoring of China, West China Second University Hospital, Sichuan University, Chengdu, China.|Department of Epidemiology and Health Statistics, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: National Center for Birth Defect Monitoring of China, West China Second University Hospital, Sichuan University, Chengdu, China.|Laboratory of Molecular Epidemiology for Birth Defects, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Center for Birth Defect Monitoring of China, West China Second University Hospital, Sichuan University, Chengdu, China.|Laboratory of Molecular Epidemiology for Birth Defects, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Ultrasound, Shenzhen Maternity &Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
authors.affiliation: Department of Ultrasound, Maternal and Child Healthcare Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
authors.forename: Xiaoxian
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Obstetrics &Gynecology, Fujian Provincial Maternal and Child Healthcare Hospital, Fuzhou, Fujian, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Ultrasound, Sichuan Provincial Maternal and Child Healthcare Hospital, Chengdu, Sichuan, China.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: National Center for Birth Defect Monitoring of China, West China Second University Hospital, Sichuan University, Chengdu, China.|Laboratory of Molecular Epidemiology for Birth Defects, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Li
authors.affiliation: National Office for Maternal and Child Health Surveillance, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Hubei Provincial Maternal and Child Healthcare Hospital, Wuhan, China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Chen
authors.affiliation: National Center for Birth Defect Monitoring of China, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Deng
authors.affiliation: National Center for Birth Defect Monitoring of China, West China Second University Hospital, Sichuan University, Chengdu, China.|Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006197:Hair / Q000737:chemistry; D006330:Heart Defects, Congenital / Q000145:classification / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009538:Nicotine / Q000032:analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D009538:Nicotine; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human