Journal article
A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants
Pediatric research, Vol.81(4), pp.582-588
04/2017
DOI: 10.1038/pr.2016.260
PMCID: PMC5714513
PMID: 27893720
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.
Details
- Title: Subtitle
- A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants
- Creators
- Venkatesh Sampath - Department of Pediatrics, Children's Mercy, Kansas City, MissouriVineet Bhandari - Current affiliation: St. Christopher's Hospital for Children/Drexel University College of Medicine, Philadelphia, PAJessica Berger - Current affiliation: John Hopkins University School of Medicine, Baltimore, MarylandDaniel Merchant - Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WisconsinLiyun Zhang - Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WisconsinMihoko Ladd - Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, CanadaHeather Menden - Department of Pediatrics, Children's Mercy, Kansas City, MissouriJeffery Garland - Department of Pediatrics, St Joseph Hospital, Milwaukee, WisconsinNamasivayam Ambalavanan - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AlabamaNeil Mulrooney - Department of Pediatrics, Children's Hospitals and Clinics of Minnesota, Minneapolis, MinnesotaMichael Quasney - Department of Pediatrics, University of Michigan, Ann Harbor, MichiganJohn Dagle - Department of Pediatrics, Iowa Children's Hospital, Iowa City, IowaPascal M Lavoie - Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, CanadaPippa Simpson - Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WisconsinMary Dahmer - Department of Pediatrics, University of Michigan, Ann Harbor, Michigan
- Resource Type
- Journal article
- Publication Details
- Pediatric research, Vol.81(4), pp.582-588
- Publisher
- United States
- DOI
- 10.1038/pr.2016.260
- PMID
- 27893720
- PMCID
- PMC5714513
- ISSN
- 0031-3998
- eISSN
- 1530-0447
- Grant note
- KL2 TR000056 / NCATS NIH HHS
- Language
- English
- Date published
- 04/2017
- Academic Unit
- Stead Family Department of Pediatrics; Epidemiology; Biochemistry and Molecular Biology; Neonatology
- Record Identifier
- 9984025285202771
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