Polymorphisms in inflammatory genes are associated with term small for gestational age and preeclampsia

Quaker E. Harmon, Stephanie M. Engel, Michael C. Wu, Thomas M. Moran, Jingchun Luo, Alison M. Stuebe, Christy L. Avery, Andrew F. Olshan

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Problem: Inflammatory biomarkers are associated with preeclampsia (PE) and poor fetal growth; however, genetic epidemiologic studies have been limited by reduced gene coverage and the exclusion of African American mothers. Method of study: Cases and controls (N = 1646) from a pregnancy cohort were genotyped for 503 tagSNPs in 40 genes related to inflammation. Gene-set analyses were stratified by race and were followed by a single SNP analysis within significant gene sets. Results: Gene-level associations were found for IL6 and KLRD1 for term small for gestational age (SGA) among African Americans. LTA/TNF and TBX21 were associated with PE among European Americans. The strongest association was for PE among European Americans for an upstream regulator of TNF with RR = 1.8 (95% CI 1.1-2.7). Conclusion: Although previous studies have suggested null associations, increased tagging and stratification by genetic ancestry suggests important associations between IL6 and term SGA for African Americans, and a TNF regulator and PE among European Americans (N = 149).

Original languageEnglish
Pages (from-to)472-484
Number of pages13
JournalAmerican Journal of Reproductive Immunology
Volume71
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • African Americans
  • Genetic association studies
  • Preeclampsia
  • Pregnancy
  • Small for gestational age

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