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Genetic regulation of amniotic fluid TNF-alpha and soluble TNF receptor concentrations affected by race and preterm birth

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Abstract

Racial disparity in spontaneous preterm birth (PTB) between African Americans and Caucasians in the US is unexplained, but is probably related to differences in amniotic fluid (AF) inflammatory cytokine profiles. Therefore, this study analyzed the association of 34 single nucleotide polymorphisms (SNPs) in TNF-α and its receptor genes (TNFR1 and TNFR2) with AF TNF-α and soluble TNF receptor (R1 and R2) concentrations in PTB. Samples consisted of African American and Caucasian cases (PTB), and controls (term birth) for which both cytokine, and maternal and fetal genotype data were available. Analyses were performed with genotype, case, and maker-status interaction in the model for log transformed cytokine concentrations. In Caucasians, two interactions between genotype and pregnancy outcome associated with cytokine concentrations, whereas 14 gene variants in African Americans showed interactions with pregnancy outcome, and 13 showed association with genetic markers. In conclusion, cytokine concentrations in African American preterm births can be partially explained by interactions between pregnancy outcome, SNPs and infection. This does not appear to be the case in Caucasians. These findings may be important in understanding disparity in rates of PTB between the two populations.

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Acknowledgments

This study was supported by a grant from Elsass foundation, Denmark (to R.M.) Thrasher Research Funds (to S.J.F), and by the Maternal Fetal Group, Nashville, TN, USA.

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Authors and Affiliations

  1. The Perinatal Research Center, 2300 Patterson Street, Nashville, TN, 37203, USA

    Ramkumar Menon, Nicole Morgan, Salvatore J. Lombardi & Stephen J. Fortunato

  2. Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

    Ramkumar Menon

  3. Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA

    Digna R. Velez & Scott M. Williams

  4. Division of Human Genomics, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA

    Scott M. Williams

Authors
  1. Ramkumar Menon
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  2. Digna R. Velez
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  3. Nicole Morgan
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  4. Salvatore J. Lombardi
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  5. Stephen J. Fortunato
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  6. Scott M. Williams
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Correspondence to Ramkumar Menon.

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Menon, R., Velez, D.R., Morgan, N. et al. Genetic regulation of amniotic fluid TNF-alpha and soluble TNF receptor concentrations affected by race and preterm birth. Hum Genet 124, 243–253 (2008). https://doi.org/10.1007/s00439-008-0547-z

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  • DOI: https://doi.org/10.1007/s00439-008-0547-z

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