title: Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery: new insights on GxE interactions and pathogenic pathways.
abstract: Preterm delivery (PTD, <37 weeks of gestation) is a significant clinical and public health problem. Previously, we reported that maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 synergistically increase the risk of low birth weight. This study investigates the relationship between maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 with preterm delivery (PTD) as a whole and preterm subgroups. This case-control study included 1,749 multi-ethnic mothers (571 with PTD and 1,178 controls) enrolled at Boston Medical Center. After adjusting covariates, regression analyses were performed to identify individual and joint associations of maternal smoking, two functional variants of CYP1A1 and GSTT1 with PTD. We observed a moderate effect of maternal smoking on PTD (OR = 1.6; 95% CI: 1.1-2.2). We found that compared to non-smoking mothers with low-risk genotypes, there was a significant joint association of maternal smoking, CYP1A1 (Aa/aa) and GSTT1 (absent) genotypes with gestational age (beta = -3.37; SE = 0.86; P = 9 x 10(-5)) and with PTD (OR = 5.8; 95% CI: 2.0-21.1), respectively. Such joint association was particularly strong in certain preterm subgroups, including spontaneous PTD (OR = 8.3; 95% CI: 2.7-30.6), PTD < 32 weeks (OR = 11.1; 95% CI: 2.9-47.7), and PTD accompanied by histologic chorioamnionitis (OR = 15.6; 95% CI: 4.1-76.7). Similar patterns were observed across ethnic groups. Taken together, maternal smoking significantly increased the risk of PTD among women with high-risk CYP1A1 and GSTT1 genotypes. Such joint associations were strongest among PTD accompanied by histologic chorioamnionitis.
authors.affiliation: Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. htsai@childrensmemorial.org
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Karen
authors.initials: K
authors.lastname: Mestan
authors.forename: Yunxian
authors.initials: Y
authors.lastname: Yu
authors.forename: Shanchun
authors.initials: S
authors.lastname: Zhang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Fang
authors.forename: Colleen
authors.initials: C
authors.lastname: Pearson
authors.forename: Katherin
authors.initials: K
authors.lastname: Ortiz
authors.forename: Barry
authors.initials: B
authors.lastname: Zuckerman
authors.forename: Howard
authors.initials: H
authors.lastname: Bauchner
authors.forename: Sandra
authors.initials: S
authors.lastname: Cerda
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Stubblefield
authors.forename: Xiping
authors.initials: X
authors.lastname: Xu
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D002821:Chorioamnionitis / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008660:Metabolism / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011247:Pregnancy; D047928:Premature Birth / Q000201:enzymology / Q000209:etiology* / Q000235:genetics*; D012044:Regression Analysis; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D019363:Cytochrome P-450 CYP1A1; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase