Racial disparity in maternal-fetal genetic epistasis in spontaneous preterm birth

Stephen J. Fortunato, Ramkumar Menon, Digna R. Velez, Poul Thorsen, Scott M. Williams

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective: To understand the differences in genetic interactions among tumor necrosis factor-alpha, interleukin-6 and their receptor gene variants between black and white patients in spontaneous preterm birth. Study Design: Maternal and fetal DNA (n = 1195) were collected from cases (preterm birth < 36 weeks' gestation; n = 448), controls (> 37 weeks' gestation; n = 747), and genotyped for single nucleotide polymorphisms in tumor necrosis factor-alpha, tumor necrosis factor receptor 1, and tumor necrosis factor receptor 2, interleukin-6, and interleukin-6 receptor loci. Multifactor dimensionality reduction analysis was used to test all single and multilocus combinations for the ability to predict pregnancy outcome. Results: In white patients, multilocus interactions in maternal DNA between single nucleotide polymorphisms at -7227 (interleukin-6), 22,215 (interleuki-6 receptor) and -3448 (tumor necrosis factor-alpha) was predictive of approximately 59.1% (P < .02; odds ratio, 2.3 [95% confidence interval = 1.6-3.4]) of pregnancy outcome. In white fetal DNA and black maternal DNA, no significant interactive models were observed. In black patients, the best epistatic model was in fetal DNA between single nucleotide polymorphisms at 17,691 (tumor necrosis factor-receptor 1) and at -3448 (tumor necrosis factor-alpha) and was predictive of pregnancy outcome 68.3% of the time (P < .01; odds ratio, 5.0 [95% confidence interval = 2.6-9.6]). Conclusion: Analyses of multilocus interactions found/associated different models in black and white patients in both maternal and fetal DNA with preterm birth as outcome. Significant maternal-fetal interactions were not detected in either race.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume198
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Fingerprint

Genetic Epistasis
Premature Birth
Mothers
DNA
Pregnancy Outcome
Tumor Necrosis Factor-alpha
Single Nucleotide Polymorphism
Interleukin-6 Receptors
Tumor Necrosis Factor Receptors
Interleukin-6
Multifactor Dimensionality Reduction
Odds Ratio
Confidence Intervals
Receptors, Tumor Necrosis Factor, Type II
Pregnancy

Keywords

  • African American women
  • gene-gene interactions
  • inflammatory cytokines
  • multifactor dimensionality reduction
  • prematurity rate
  • preterm delivery
  • white women

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Racial disparity in maternal-fetal genetic epistasis in spontaneous preterm birth. / Fortunato, Stephen J.; Menon, Ramkumar; Velez, Digna R.; Thorsen, Poul; Williams, Scott M.

In: American Journal of Obstetrics and Gynecology, Vol. 198, No. 6, 06.2008.

Research output: Contribution to journalArticle

Fortunato, Stephen J. ; Menon, Ramkumar ; Velez, Digna R. ; Thorsen, Poul ; Williams, Scott M. / Racial disparity in maternal-fetal genetic epistasis in spontaneous preterm birth. In: American Journal of Obstetrics and Gynecology. 2008 ; Vol. 198, No. 6.
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