Medical College of Wisconsin
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A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants. Pediatr Res 2017 Apr;81(4):582-588

Date

11/29/2016

Pubmed ID

27893720

Pubmed Central ID

PMC5714513

DOI

10.1038/pr.2016.260

Scopus ID

2-s2.0-85017599086 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Author List

Sampath V, Bhandari V, Berger J, Merchant D, Zhang L, Ladd M, Menden H, Garland J, Ambalavanan N, Mulrooney N, Quasney M, Dagle J, Lavoie PM, Simpson P, Dahmer M

Author

Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alleles
Autophagy
Autophagy-Related Proteins
Carrier Proteins
Cohort Studies
Enterocolitis, Necrotizing
Female
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Infant, Newborn
Infant, Premature
Polymorphism, Single Nucleotide