Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome 8.

Journal Article (Journal Article)

BackgroundTwin studies suggest that genetic factors may account for up to 50% increased risk for necrotizing enterocolitis (NEC), but genome-wide association studies for NEC are lacking.MethodsGenotyping was done on Illumina BeadChip, followed by analysis using PLINK with logistic regression under an additive model.ResultsAmong 751 extremely-low-birth-weight (<1,000 g, >401 g) neonates, 30 had surgical NEC. Two hundred and sixty-one single-nucleotide polymorphisms (SNPs) showed association with NEC at P<0.05, of which 35 were significant at P<10-7. Minor allele(s) in a cluster of SNPs spanning a 43-kb region of chromosome 8 (8q23.3) conferred an odds ratio of 4.72 (95% confidence interval (CI): 2.51-8.88) for elevated risk of NEC. Two smaller clusters on chromosome 14 and chromosome 11 exhibited P values of 10-7-10-8. The chromosome 8 cluster is in an intergenic region between CUB and Sushi multiple domains 3 (-1.43 Mb) and trichorhinophalangeal syndrome I (+542 kb). RNA sequencing in this region identified a potential novel open-reading frame corresponding to a long interspersed element-1 retrotransposable element.ConclusionGenetic variation in an intergenic region of chromosome 8 is associated with increased risk for NEC with a mechanism that is yet to be identified.

Full Text

Duke Authors

Cited Authors

  • Jilling, T; Ambalavanan, N; Cotten, CM; Martin, CA; Maheshwari, A; Schibler, K; Levy, J; Page, GP

Published Date

  • May 2018

Published In

Volume / Issue

  • 83 / 5

Start / End Page

  • 943 - 953

PubMed ID

  • 29538362

Pubmed Central ID

  • PMC6053310

Electronic International Standard Serial Number (EISSN)

  • 1530-0447

Digital Object Identifier (DOI)

  • 10.1038/pr.2018.33


  • eng

Conference Location

  • United States