Association of polymorphisms in natural killer cell-related genes with Preterm Birth

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Inflammation is implicated in preterm birth, but genetic studies of inflammatory genes have yielded inconsistent results. Maternal DNA from 1,646 participants in the Pregnancy, Infection, and Nutrition Cohort, enrolled in Orange and Wake counties, North Carolina (1995-2005), were genotyped for 432 tag single-nucleotide polymorphisms (SNPs) in 30 candidate genes. Gene-level and SNP associations were modeled within strata of genetic ancestry. Six genes were associated with preterm birth among European Americans: interleukin 12A (IL12A); colony-stimulating factor 2 (CSF2); interferon γ receptor 2 (IFNGR2); killer cell immunoglobulin-like receptor, three domain, long cytoplasmic tail, 2 (KIR3DL2); interleukin 4 (IL4); and interleukin 13 (IL13). Of these, relatively strong single-SNP associations were seen in IFNGR2 and KIR3DL2. Among the 4 genes related to natural killer cell function, 2 (IL12A and CSF2) were consistently associated with reduced risk of prematurity for both European and African Americans. SNPs tagging a locus control region for IL4 and IL13 were associated with an increased risk of spontaneous preterm birth for European Americans (rs3091307; risk ratio = 1.9; 95% confidence interval: 1.4, 2.5). Although gene-level associations were detected only in European Americans, single-SNP associations among European and African Americans were often similar in direction, though estimated with less precision among African Americans. In conclusion, we identified novel associations between variants in the natural killer cell immune pathway and prematurity in this biracial US population.

Original languageEnglish
Pages (from-to)1208-1218
Number of pages11
JournalAmerican Journal of Epidemiology
Volume178
Issue number8
DOIs
StatePublished - 15 Oct 2013
Externally publishedYes

Keywords

  • African Americans; European Continental Ancestry Group; genetics
  • genetic association studies
  • inflammation
  • natural killer cells
  • premature birth

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