title: Are Immune Modulating Single Nucleotide Polymorphisms Associated with Necrotizing Enterocolitis?
abstract: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over 7 times more likely to have Stage III disease (p = 0.011; OR = 7.13, (95% CI 1.56-32.52). Neonates with TGFβ-1 (rs2241712) had a decreased incidence of NEC-related perforation (p = 0.044; OR = 0.28, 95% CI: 0.08-0.97) and an increased incidence of mortality (p = 0.049; OR = 2.99, 95% CI: 1.01 - 8.86). TRIM21 (rs660) was associated with NEC-related intestinal perforation (p = 0.038; OR = 4.65, 95% CI 1.09-19.78). In premature Caucasian neonates, the functional SNP IL-6 (rs1800795) is associated with both the development and increased severity of NEC. TRIM21 (rs660) and TGFβ-1 (rs2241712) were associated with NEC- related perforation in all neonates in the cohort. These findings suggest a possible genetic role in the development of NEC.
authors.affiliation: Division of General and Thoracic Surgery, Children's National Health System, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Ashanti L
authors.initials: AL
authors.lastname: Franklin
authors.affiliation: Division of Neonatology, Children's National Health System, Washington, DC, Department of Pediatrics, The George Washington School of Medicine and Health Sciences, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Mariam
authors.initials: M
authors.lastname: Said
authors.affiliation: Division of General and Thoracic Surgery, Children's National Health System, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Clint D
authors.initials: CD
authors.lastname: Cappiello
authors.affiliation: Children's Research Institute, Children's National Health System, Washington, DC, Department of Pediatrics, The George Washington School of Medicine and Health Sciences, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.affiliation: Sheikh Zayed Institute, Children's National Health System, Washington, DC, Department of Pediatrics, The George Washington School of Medicine and Health Sciences, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Tatari-Calderone
authors.affiliation: Sheikh Zayed Institute, Children's National Health System, Washington, DC, Department of Pediatrics, The George Washington School of Medicine and Health Sciences, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Vukmanovic
authors.affiliation: Division of Neonatology, Children's National Health System, Washington, DC, Department of Pediatrics, The George Washington School of Medicine and Health Sciences, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Khodayar
authors.initials: K
authors.lastname: Rais-Bahrami
authors.affiliation: Department Laboratory Medicine, Children's National Health System Washington, DC, Department of Pediatrics, The George Washington School of Medicine and Health Sciences, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Naomi L C
authors.initials: NL
authors.lastname: Luban
authors.affiliation: Department of Genetic Medicine, Children's National Health System, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Devaney
authors.affiliation: Division of General and Thoracic Surgery, Children's National Health System, Washington, DC, Department of Pediatrics, The George Washington School of Medicine and Health Sciences, 111 Michigan Ave NW, Washington, DC 20010.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Sandler
mesh_terms: D020345:Enterocolitis, Necrotizing / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000276:immunology*; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology; D000099207:SS-A Antigen
chemical_list: D015850:Interleukin-6; D012261:Ribonucleoproteins; D053773:Transforming Growth Factor beta1; D000099207:SS-A Antigen; C508600:IL6 protein, human; C508960:TGFB1 protein, human