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

Hui Ju Tsai, Xin Liu, Karen Mestan, Yunxian Yu, Shanchun Zhang, Yaping Fang, Colleen Pearson, Katherin Ortiz, Barry Zuckerman, Howard Bauchner, Sandra Cerda, Phillip G. Stubblefield, Xiping Xu, Xiaobin Wang

Research output: Contribution to journalArticle

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 (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.

Original languageEnglish (US)
Pages (from-to)359-369
Number of pages11
JournalHuman genetics
Volume123
Issue number4
DOIs
StatePublished - May 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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  • Cite this

    Tsai, H. J., Liu, X., Mestan, K., Yu, Y., Zhang, S., Fang, Y., Pearson, C., Ortiz, K., Zuckerman, B., Bauchner, H., Cerda, S., Stubblefield, P. G., Xu, X., & Wang, X. (2008). Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery: New insights on G × E interactions and pathogenic pathways. Human genetics, 123(4), 359-369. https://doi.org/10.1007/s00439-008-0485-9