Document Detail

The NFKB1 (g.-24519delATTG) Variant is Associated with Necrotizing Enterocolitis (NEC) in Premature Infants.
MedLine Citation:
PMID:  21529841     Owner:  NLM     Status:  Publisher    
OBJECTIVE: While it is known that gene-environment interactions contribute to necrotizing enterocolitis (NEC) pathogenesis, characterization of genetic risk-factors that can predict NEC in preterm infants remains nascent. We hypothesized that altered intestinal immune responses arising from sequence variation in the toll-like receptor (TLR) pathway genes contribute to NEC susceptibility. MATERIALS AND METHODS: Very low birth weight (VLBW) infants were recruited prospectively in a multi-center, cohort study involving collection of blood samples along with collation of clinical information. DNA obtained from blood samples was used to genotype nine single nucleotide polymorphisms (SNPs) in eight TLR pathway genes by single-base extension. Prevalence of the variant allele was compared between cases and controls using Fisher's exact test. RESULTS: In our cohort of 271 infants, 15 infants (5.6%) developed NEC, and five died from it. Infants with NEC were less mature (P < 0.001), and were more likely to be African-American (P = 0.007). SNPs in the TLR2, TLR4, TLR5, TLR9, IRAK1, and TIRAP genes were not associated with NEC. The NFKB1 (g.-24519delATTG) variant was present in all infants with NEC but only in 65% of infants without NEC (P = 0.003), while the NFKBIA (g.-1004A>G) variant was present in 13.3% of infants with NEC but in 49% of infants without NEC (P = 0.007). After correcting for multiple comparisons, the NFKB1 and NFKBIA variants remained associated with NEC (P < 0.05). CONCLUSIONS: These data suggest that TLR genetic variants can alter susceptibility to NEC in VLBW infants and support the hypothesis that genetically programmed differences in the innate immune response contribute to NEC pathogenesis.
Venkatesh Sampath; Min Le; Laura Lane; Aloka L Patel; Jonathan D Cohen; Pippa M Simpson; Jeffery S Garland; Ronald N Hines
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-1
Journal Detail:
Title:  The Journal of surgical research     Volume:  -     ISSN:  1095-8673     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-5-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, Wisconsin.
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