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

Am J Reprod Immunol. 2014 May;71(5):472-84. doi: 10.1111/aji.12241. Epub 2014 Apr 4.

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).

Keywords: African Americans; genetic association studies; preeclampsia; pregnancy; small for gestational age.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Adult
  • Black or African American
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age*
  • Inflammation / ethnology
  • Inflammation / genetics
  • Inflammation / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Lymphotoxin-alpha / genetics
  • Lymphotoxin-alpha / immunology
  • NK Cell Lectin-Like Receptor Subfamily D / genetics
  • NK Cell Lectin-Like Receptor Subfamily D / immunology
  • Polymorphism, Single Nucleotide*
  • Pre-Eclampsia / ethnology*
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / immunology
  • Pregnancy
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology
  • United States / epidemiology
  • White People

Substances

  • Adaptor Proteins, Signal Transducing
  • IL6 protein, human
  • Interleukin-6
  • KLRD1 protein, human
  • Lymphotoxin-alpha
  • NK Cell Lectin-Like Receptor Subfamily D
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • TBKBP1 protein, human