Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome eight
BACKGROUND: Twin studies suggest that genetic factors may account for up to 50% increased risk for necrotizing enterocolitis (NEC), but genome-wide association studies (GWAS) for NEC are lacking.
METHODS: Genotyping was done on Illumina BeadChip, followed by analysis using PLINK with logistic regression under an additive model.
RESULTS: Among 751 extremely low birth weight (<1000 g, >401 g) neonates, 30 had surgical NEC. 261 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 a cluster of SNPs spanning a 43 Kb region of chromosome 8 (8q23.3) conferred an odds ratio of 4.72 (95% CI 2.51-8.88) for elevated risk of NEC. Two smaller clusters on chromosome 14 and chromosome 11 exhibited P values 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 (LINE-1) retrotransposable element.
CONCLUSION: Genetic variation in an intergenic region of chromosome 8 is associacted with increased risk for NEC with a mechanismthat is yet to be identified.Pediatric Research accepted article preview online, 14 March 2018. doi:10.1038/pr.2018.33.
Jilling, T., Ambalavanan, N., Cotten, C. M., Martin, C. A., Maheshwari, A., Schibler, K., ... Page, G. P. (2018). Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome eight. Pediatric Research, 83(5), 943–953. DOI: 10.1038/pr.2018.33