Skip to main content

Advertisement

Log in

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

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Anonymous (2006a) Preterm birth: cause, consequences, and prevention. In: press Tna (ed). Institute of medicine of the national academies (Committee on understanding premature birth and assuring healthy outcomes board on health sciences policy). Washington DC

  • Anonymous (2006b) Preterm birth: crisis and opportunity. Lancet 368:339

  • Bartsch H (1996) DNA adducts in human carcinogenesis: etiological relevance and structure–activity relationship. Mutat Res 340:67–79

    PubMed  Google Scholar 

  • Bartsch H, Rojas M, Alexandrov K, Camus AM, Castegnaro M, Malaveille C, Anttila S, Hirvonen K, Husgafvel-Pursiainen K, Hietanen E et al (1995) Metabolic polymorphism affecting DNA binding and excretion of carcinogens in humans. Pharmacogenetics 5 (Spec No):S84–S90

    Article  PubMed  CAS  Google Scholar 

  • Benjamini Y, Yekutieli D (2001) The control of the false discovery rate in multiple testing under dependency. Ann Stat 29:1165–1188

    Article  Google Scholar 

  • Bush PG, Mayhew TM, Abramovich DR, Aggett PJ, Burke MD, Page KR (2000) Maternal cigarette smoking and oxygen diffusion across the placenta. Placenta 21:824–833

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Hu Y, Yang F, Li Z, Wu B, Fang Z, Li J, Wang L (2005) Cytochrome P450 gene polymorphisms and risk of low birth weight. Genet Epidemiol 28:368–375

    Article  PubMed  Google Scholar 

  • Cnattingius S (2004) The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine Tob Res 6(Suppl 2):S125–S140

    Article  PubMed  Google Scholar 

  • Crider KS, Whitehead N, Buus RM (2005) Genetic variation associated with preterm birth: a HuGE review. Genet Med 7:593–604

    PubMed  CAS  Google Scholar 

  • Engle WA, Tomashek KM, Wallman C (2007) “Late-preterm” infants: a population at risk. Pediatrics 120:1390–1401

    Article  PubMed  Google Scholar 

  • Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164:1567–1587

    PubMed  CAS  Google Scholar 

  • George L, Granath F, Johansson AL, Cnattingius S (2006) Self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy. Acta Obstet Gynecol Scand 85:1331–1337

    Article  PubMed  CAS  Google Scholar 

  • Gupta M, Mestan KK, Martin CR, Pearson C, Ortiz K, Fu L, Stubblefield P, Cerda S, Kasznica JM, Wang X (2007) Impact of clinical and histologic correlates of maternal and fetal inflammatory response on gestational age in preterm births. J Matern Fetal Neonatal Med 20:39–46

    Article  PubMed  Google Scholar 

  • Haddad JJ (2002) Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive transcription factors. Cell Signal 14:879–897

    Article  PubMed  CAS  Google Scholar 

  • Hamill PV, Drizd TA, Johnson CL, Reed RB, Roche AF, Moore WM (1979) Physical growth: National Center for Health Statistics percentiles. Am J Clin Nutr 32:607–629

    PubMed  CAS  Google Scholar 

  • Hayashi S, Watanabe J, Kawajiri K (1992) High susceptibility to lung cancer analyzed in terms of combined genotypes of P450IA1 and Mu-class glutathione S-transferase genes. Jpn J Cancer Res 83:866–870

    PubMed  CAS  Google Scholar 

  • Irani K (2000) Oxidant signaling in vascular cell growth, death, and survival: a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ Res 87:179–183

    PubMed  CAS  Google Scholar 

  • Katoh T, Inatomi H, Nagaoka A, Sugita A (1995) Cytochrome P4501A1 gene polymorphism and homozygous deletion of the glutathione S-transferase M1 gene in urothelial cancer patients. Carcinogenesis 16:655–657

    Article  PubMed  CAS  Google Scholar 

  • Klebanoff MA, Levine RJ, Morris CD, Hauth JC, Sibai BM, Ben Curet L, Catalano P, Wilkins DG (2001) Accuracy of self-reported cigarette smoking among pregnant women in the 1990s. Paediatr Perinat Epidemiol 15:140–143

    Article  PubMed  CAS  Google Scholar 

  • Kramer MS, Platt R, Yang H, Joseph KS, Wen SW, Morin L, Usher RH (1998) Secular trends in preterm birth: a hospital-based cohort study. JAMA 280:1849–1854

    Article  PubMed  CAS  Google Scholar 

  • Kriek E, Rojas M, Alexandrov K, Bartsch H (1998) Polycyclic aromatic hydrocarbon-DNA adducts in humans: relevance as biomarkers for exposure and cancer risk. Mutat Res 400:215–231

    PubMed  CAS  Google Scholar 

  • Landi MT, Bertazzi PA, Shields PG, Clark G, Lucier GW, Garte SJ, Cosma G, Caporaso NE (1994) Association between CYP1A1 genotype, mRNA expression and enzymatic activity in humans. Pharmacogenetics 4:242–246

    Article  PubMed  CAS  Google Scholar 

  • Macaubas C, de Klerk NH, Holt BJ, Wee C, Kendall G, Firth M, Sly PD, Holt PG (2003) Association between antenatal cytokine production and the development of atopy and asthma at age 6 years. Lancet 362:1192–1197

    Article  PubMed  CAS  Google Scholar 

  • Macones GA, Parry S, Elkousy M, Clothier B, Ural SH, Strauss JF III (2004) A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth. Am J Obstet Gynecol 190:1504–1508 discussion 3A

    Article  PubMed  CAS  Google Scholar 

  • Magnusson CG (1986) Maternal smoking influences cord serum IgE and IgD levels and increases the risk for subsequent infant allergy. J Allergy Clin Immunol 78:898–904

    Article  PubMed  CAS  Google Scholar 

  • Mathews TJ, Menacker F, MacDorman MF (2004) Infant mortality statistics from the 2002 period: linked birth/infant death data set. Natl Vital Stat Rep 53:1–29

    PubMed  CAS  Google Scholar 

  • Muller J, Petkovic M, Schiller J, Arnold K, Reichl S, Arnhold J (2002) Effects of lysophospholipids on the generation of reactive oxygen species by fMLP- and PMA-stimulated human neutrophils. Luminescence 17:141–149

    Article  PubMed  CAS  Google Scholar 

  • Nakachi K, Imai K, Hayashi S, Kawajiri K (1993) Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Res 53:2994–2999

    PubMed  CAS  Google Scholar 

  • Noakes PS, Holt PG, Prescott SL (2003) Maternal smoking in pregnancy alters neonatal cytokine responses. Allergy 58:1053–1058

    Article  PubMed  CAS  Google Scholar 

  • Noakes PS, Hale J, Thomas R, Lane C, Devadason SG, Prescott SL (2006) Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses. Eur Respir J 28:721–729

    Article  PubMed  CAS  Google Scholar 

  • Nukui T, Day RD, Sims CS, Ness RB, Romkes M (2004) Maternal/newborn GSTT1 null genotype contributes to risk of preterm, low birthweight infants. Pharmacogenetics 14:569–576

    Article  PubMed  CAS  Google Scholar 

  • Palackal NT, Lee SH, Harvey RG, Blair IA, Penning TM (2002) Activation of polycyclic aromatic hydrocarbon trans-dihydrodiol proximate carcinogens by human aldo-keto reductase (AKR1C) enzymes and their functional overexpression in human lung carcinoma (A549) cells. J Biol Chem 277:24799–24808

    Article  PubMed  CAS  Google Scholar 

  • Palli D, Saieva C, Gemma S, Masala G, Gomez-Miguel MJ, Luzzi I, D’Errico M, Matullo G, Ozzola G, Manetti R, Nesi G, Sera F, Zanna I, Dogliotti E, Testai E (2005) GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high-risk italian population. Int J Cancer 115:284–289

    Article  PubMed  CAS  Google Scholar 

  • Peacock JL, Cook DG, Carey IM, Jarvis MJ, Bryant AE, Anderson HR, Bland JM (1998) Maternal cotinine level during pregnancy and birthweight for gestational age. Int J Epidemiol 27:647–656

    Article  PubMed  CAS  Google Scholar 

  • Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB (1994) Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300(Pt 1):271–276

    PubMed  CAS  Google Scholar 

  • Pennell CE, Jacobsson B, Williams SM, Buus RM, Muglia LJ, Dolan SM, Morken NH, Ozcelik H, Lye SJ, Relton C (2007) Genetic epidemiologic studies of preterm birth: guidelines for research. Am J Obstet Gynecol 196:107–118

    Article  PubMed  Google Scholar 

  • Pollack H, Lantz PM, Frohna JG (2000) Maternal smoking and adverse birth outcomes among singletons and twins. Am J Public Health 90:395–400

    Article  PubMed  CAS  Google Scholar 

  • Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959

    PubMed  CAS  Google Scholar 

  • Ryder MI (2007) The influence of smoking on host responses in periodontal infections. Periodontol 2000 43:267–277

    Article  PubMed  Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory, Cold Spring Harbor

    Google Scholar 

  • Seidegard J, Vorachek WR, Pero RW, Pearson WR (1988) Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion. Proc Natl Acad Sci USA 85:7293–7297

    Article  PubMed  CAS  Google Scholar 

  • Shah NR, Bracken MB (2000) A systematic review and meta-analysis of prospective studies on the association between maternal cigarette smoking and preterm delivery. Am J Obstet Gynecol 182:465–472

    Article  PubMed  CAS  Google Scholar 

  • Shiverick KT, Salafia C (1999) Cigarette smoking and pregnancy. I: Ovarian, uterine and placental effects. Placenta 20:265–272

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Tager IB, Van Vunakis H, Speizer FE, Hanrahan JP (1997) Maternal smoking during pregnancy, urine cotinine concentrations, and birth outcomes: a prospective cohort study. Int J Epidemiol 26:978–988

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Zuckerman B, Kaufman G, Wise P, Hill M, Niu T, Ryan L, Wu D, Xu X (2001) Molecular epidemiology of preterm delivery: methodology and challenges. Paediatr Perinat Epidemiol 15(Suppl 2):63–77

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Zuckerman B, Pearson C, Kaufman G, Chen C, Wang G, Niu T, Wise PH, Bauchner H, Xu X (2002) Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. JAMA 287:195–202

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Feng Y, Zhang Y, Zhou H, Jiang S, Niu T, Wei LJ, Xu X, Xu X, Wang X (2006) Prolylcarboxypeptidase gene, chronic hypertension, and risk of preeclampsia. Am J Obstet Gynecol 195:162–171

    Article  PubMed  CAS  Google Scholar 

  • Wigginton JE, Cutler DJ, Abecasis GR (2005) A note on exact tests of Hardy–Weinberg equilibrium. Am J Hum Genet 76:887–893

    Article  PubMed  CAS  Google Scholar 

  • Willwerth BM, Schaub B, Tantisira KG, Gold DR, Palmer LJ, Litonjua AA, Perkins DL, Schroeter C, Gibbons FK, Gillman MW, Weiss ST, Finn PW (2006) Prenatal, perinatal, and heritable influences on cord blood immune responses. Ann Allergy Asthma Immunol 96:445–453

    Article  PubMed  Google Scholar 

  • Xu X, Kelsey KT, Wiencke JK, Wain JC, Christiani DC (1996) Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev 5:687–692

    PubMed  CAS  Google Scholar 

  • Yang N, Li H, Criswell LA, Gregersen PK, Alarcon-Riquelme ME, Kittles R, Shigeta R, Silva G, Patel PI, Belmont JW, Seldin MF (2005) Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine. Hum Genet 118: 382–392

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to two reviewers for the very helpful comments. The study was supported in part by grants from the National Institute of Child Health and Human Development (R01 HD41702), National Institute of Environmental Health Sciences (R01ES11682, R21ES11666), March of Dimes Birth Defects Foundation (20-FY98−0701, 20-FY02-56 and #21-FY07-605) and NICHD (K24 HD 042489).We thank the nursing staff of Labor and Delivery at Boston Medical Center for their continuous support and assistance to the study and Lingling Fu for data management, and Ann Ramsay for administrative support. We would like to particularly thank the outstanding expert consultants of the BMC Preterm Study team: Drs. Paul Wise, Jerome Klein, John M. Kasznica, and Milton Kotelchuck. Finally, we thank all of the participating mothers and their families.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hui-Ju Tsai.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary tables (DOC 97 kb)

Appendix: Web resources

Appendix: Web resources

The URLs for data presented herein are as follows: SNP-HWE program, Center for Statistical Genetics, University of Michigan, http://www.sph.umich.edu/csg/abecasis/Exact/index.html; R website, The R Project for Statistical Computing, http://www.r-project.org; Bioconductor website, http://www.bioconductor.org/.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsai, HJ., Liu, X., Mestan, K. et al. Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery: new insights on G×E interactions and pathogenic pathways. Hum Genet 123, 359–369 (2008). https://doi.org/10.1007/s00439-008-0485-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-008-0485-9

Keywords

Navigation