Journal article
A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants
Pediatric research, v 81(4), pp 582-588
Apr 2017
PMID: 27893720
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The genetic basis of dysfunctional immune responses in necrotizing enterocolitis (NEC) remains unknown. We hypothesized that variants in nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) and autophagy (ATG) genes modulate vulnerability to NEC.
We genotyped a multi-center cohort of premature infants with and without NEC for NOD1, NOD2, ATG16L1, CARD8, and NLRP3 variants. Chi-square tests and logistic regression were used for statistical analysis.
In our primary cohort (n = 1,015), 86 (8.5%) infants developed NEC. The A allele of the ATG16L1 (Thr300Ala) variant was associated with increased NEC (AA vs. AG vs. GG; 11.3 vs. 8.4 vs. 4.8%, P = 0.009). In regression models for NEC that adjusted for epidemiological confounders, GA (P = 0.033) and the AA genotype (P = 0.038) of ATG16L1 variant were associated with NEC. The association between the A allele of the ATG16L1 variant and NEC remained significant among Caucasian infants (P = 0.02). In a replication cohort (n = 259), NEC rates were highest among infants with the AA genotype but did not reach statistical significance.
We report a novel association between a hypomorphic variant in an autophagy gene (ATG16L1) and NEC in premature infants. Our data suggest that decreased autophagy arising from genetic variants may confer protection against NEC.
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Details
- Title
- A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants
- Creators
- Venkatesh Sampath - Children's Mercy HospitalVineet Bhandari - St. Christopher's Hospital for ChildrenJessica Berger - Johns Hopkins MedicineDaniel Merchant - Medical College of WisconsinLiyun Zhang - Medical College of WisconsinMihoko Ladd - University of British ColumbiaHeather Menden - Children's Mercy HospitalJeffery Garland - St. Joseph HospitalNamasivayam Ambalavanan - University of Alabama at BirminghamNeil Mulrooney - Children's Hospitals and Clinics of MinnesotaMichael Quasney - University of Michigan–Ann ArborJohn Dagle - Department of Pediatrics, Iowa Children's Hospital, Iowa City, Iowa.Pascal M Lavoie - University of British ColumbiaPippa Simpson - Medical College of WisconsinMary Dahmer - University of Michigan–Ann Arbor
- Publication Details
- Pediatric research, v 81(4), pp 582-588
- Publisher
- Springer Nature
- Grant note
- KL2 TR000056 / NCATS NIH HHS UL1 TR001436 / NCATS NIH HHS KL2 TR001438 / NCATS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000398652300006
- Scopus ID
- 2-s2.0-85017599086
- Other Identifier
- 991019167611104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pediatrics