Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome 8.
Pediatr Res
; 83(5): 943-953, 2018 05.
Article
in En
| MEDLINE
| ID: mdl-29538362
ABSTRACT
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:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosomes, Human, Pair 8
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Enterocolitis, Necrotizing
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Genetic Predisposition to Disease
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DNA, Intergenic
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Genome-Wide Association Study
Type of study:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Female
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Humans
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Infant
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Male
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Newborn
Language:
En
Journal:
Pediatr Res
Year:
2018
Document type:
Article
Affiliation country:
Albania