A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants.

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.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

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

doi

10.1038/pr.2016.260

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

582-588

issue

4

eissn

0031-3998

issn

1530-0447

pii

pr2016260

journal_volume

81

pub_type

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