A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants.
A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants.
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DOI：
10.1038/pr.2016.260
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发表时间：
2017-04
影响因子：
3.6
通讯作者：
Dahmer M
中科院分区：
文献类型：
--
作者：
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
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=1015), 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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ATG16L1中的THR300ALA变体与人类结直肠癌的生存率提高和I型干扰素的产生增强有关。
影响因子：
24.5
作者：
Grimm WA;Messer JS;Murphy SF;Nero T;Lodolce JP;Weber CR;Logsdon MF;Bartulis S;Sylvester BE;Springer A;Dougherty U;Niewold TB;Kupfer SS;Ellis N;Huo D;Bissonnette M;Boone DL
通讯作者：
Boone DL
影响因子：
5.3
作者：
Roberts, Rebecca L.;Van Rij, Andre M.;Jones, Gregory T.
通讯作者：
Jones, Gregory T.
影响因子：
3.6
作者：
Afrazi A;Sodhi CP;Richardson W;Neal M;Good M;Siggers R;Hackam DJ
通讯作者：
Hackam DJ
影响因子：
9
作者：
Alvarez-Lobos, M;Arostegui, JI;Panés, J
通讯作者：
Panés, J
影响因子：
29.4
作者：
Homer CR;Richmond AL;Rebert NA;Achkar JP;McDonald C
通讯作者：
McDonald C