학술논문
ITGB2 (Integrin β2) Immunomodulatory Gene Variants in Premature Infants With Necrotizing Enterocolitis
Document Type
Academic Journal
Author
Source
Journal of Pediatric Gastroenterology and Nutrition. Sep 09, 2020
Subject
Language
English
ISSN
0277-2116
Abstract
ABSTRACT: Aberrant Toll Like receptor (TLR) activation is central to necrotizing enterocolitis (NEC) pathogenesis. β2 integrins regulate TLR signaling, and Integrin β2 (ITGB2) deficiency causes TLR hyper-responsiveness. To test the hypothesis that ITGB2 genetic variants modulate NEC susceptibility, we sequenced the exonic ITGB2 locus to compare the prevalence of deleterious variants among 221 preterm infants with and without NEC. ITGB2 variants were not associated with NEC in our entire cohort [NEC (9/56) vs. controls (16/165), p = 0.19)], or in extremely low birthweight infants [ELBW, controls (7.9%) vs. NEC (18.2%); p = 0.11)] but was increased compared to the populace (4.5%, gnomad.broadinstitute.org). Combined Annotation Dependent Depletion (CADD)-predicted deleterious ITGB2 variants increased proportionately with increasing NEC severity in ELBW infants [controls (6.7%) vs. medical NEC (16.7%) vs. surgical NEC (19%), p = 0.03]. While ITGB2 variants were not associated with NEC in our preterm cohort, sub-group analysis showed a trend towards enrichment with NEC severity in ELBW infants.