Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery: new insights on G×E interactions and pathogenic pathways

• Published in: Human genetics Vol. 123; no. 4; pp. 359 - 369
• Main Authors: Tsai, Hui-Ju, Liu, Xin, Mestan, Karen, Yu, Yunxian, Zhang, Shanchun, Fang, Yaping, Pearson, Colleen, Ortiz, Katherin, Zuckerman, Barry, Bauchner, Howard, Cerda, Sandra, Stubblefield, Phillip G., Xu, Xiping, Wang, Xiaobin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.05.2008; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Birth weight; Cigarettes; Gene Function; Genes; Gestational age; Human Genetics; Medicine; Metabolic Diseases; Metabolism; Molecular Medicine; Multiple births; Original Investigation; Pediatrics; Pregnancy; Premature birth; Public health; Smoking; United States > US; Chicago Illinois; Maternal Smoking; Joint Association; GSTT1 Polymorphism; Black Mother; GSTT1 Genotype
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-008-0485-9

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 ( β  = −3.37; SE = 0.86; P  = 9 × 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.