Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms

Stephanie A Mulherin Engel, Hans Christian Erichsen, David A. Savitz, John Thorp, Stephen J. Chanock, Andrew F. Olshan

Research output: Contribution to journalArticle

Abstract

Background: Preliminary data suggest that common genetic variation in immune response genes can contribute to the risk for spontaneous preterm birth and possibly small-for-gestational age (SGA). Methods: We investigated the relationship of polymorphisms in 6 cytokine genes associated with inflammation-interleukin (IL)1α, IL1β, IL2, IL6, tumor necrosis factor (TNF), and lymphotoxin α (LTA)-with spontaneous preterm and SGA birth in a nested case-control study drawn from a prospective pregnancy cohort. Women were recruited between 24 and 29 weeks' gestation at the Wake County and University of North Carolina, Chapel Hill obstetric clinics between February 1996 and June 2000. We inferred haplotypes using the EM algorithm and the Bayesian method, PHASE. We then compared haplotype frequency distributions and implemented semi-Bayesian hierarchical logistic regression analyses to obtain odds ratio (OR) estimates and 95% confidence intervals (CIs) for each polymorphism. Results: Two haplotypes spanning the TNF/LTA genes were associated with increased risk for spontaneous preterm birth in white subjects (for the AGG haplotype, OR = 1.5 [95% CI=0.8-2.6]; for the GAC haplotype, 1.6 [0.9-2.9]). Additionally, carriers of the GAG haplotype were found to have decreased risk of spontaneous preterm birth (0.6; 0.3-1.0). The TNF(-488)A and LTA(IVS1-82)C variants, constituents of the AGG and GAC haplotypes respectively, were also strongly associated with increased risk of spontaneous preterm birth. Conclusions: Our results suggest that common genetic variants in proinflammatory cytokine genes could influence the risk for spontaneous preterm birth. Selected TNF/LTA haplotypes were associated with spontaneous preterm birth in both African-American and white subjects. Our data do not support an inflammatory etiology for SGA.

Original languageEnglish (US)
Pages (from-to)469-477
Number of pages9
JournalEpidemiology
Volume16
Issue number4
DOIs
StatePublished - Jul 2005
Externally publishedYes

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Premature Birth
Haplotypes
Cytokines
Tumor Necrosis Factor-alpha
Gestational Age
Genes
Odds Ratio
Confidence Intervals
Lymphotoxin-alpha
Pregnancy
Bayes Theorem
Interleukin-1
African Americans
Obstetrics
Interleukin-2
Case-Control Studies
Interleukin-6
Logistic Models
Regression Analysis
Parturition

ASJC Scopus subject areas

  • Epidemiology

Cite this

Engel, S. A. M., Erichsen, H. C., Savitz, D. A., Thorp, J., Chanock, S. J., & Olshan, A. F. (2005). Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms. Epidemiology, 16(4), 469-477. https://doi.org/10.1097/01.ede.0000164539.09250.31

Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms. / Engel, Stephanie A Mulherin; Erichsen, Hans Christian; Savitz, David A.; Thorp, John; Chanock, Stephen J.; Olshan, Andrew F.

In: Epidemiology, Vol. 16, No. 4, 07.2005, p. 469-477.

Research output: Contribution to journalArticle

Engel, SAM, Erichsen, HC, Savitz, DA, Thorp, J, Chanock, SJ & Olshan, AF 2005, 'Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms', Epidemiology, vol. 16, no. 4, pp. 469-477. https://doi.org/10.1097/01.ede.0000164539.09250.31
Engel, Stephanie A Mulherin ; Erichsen, Hans Christian ; Savitz, David A. ; Thorp, John ; Chanock, Stephen J. ; Olshan, Andrew F. / Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms. In: Epidemiology. 2005 ; Vol. 16, No. 4. pp. 469-477.
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