O09 - Are Functional Single Nucleotide Polymorphisms of Proinflammatory Cytokines Associated with the Development of Necrotizing Enterocolitis or Spontaneous Perforation in Premature Infants?
Author(s):
Ashanti Franklin, Mariam Said, Zoreh Tatari, Stanislav Vukmanovic, Khodayar Rais-Bahrami, Naomi Luban, Clint Cappiello, Joe Devaney, Anthony Sandler, Children's National Medical Center
Background: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency that affects approximately 10% of premature neonates. There is an increased predilection in patients of African descent and males. Functional single nucleotide polymorphisms (SNPs) in nitric oxide synthase (NOS3) or proinflammatory cytokine genes, tumor necrosis factor (TNFα), IL1B, IL6, and IL12, lead to increased cytokine expression.
Hypothesis: We evaluated whether African-American patients with polymorphisms in proinflammatory genes will have an increased susceptibility to NEC or spontaneous perforation.
Methods: Institutional Review Board approval and parental/guardian consent was obtained. Buccal swabs for DNA extraction were collected from infants that were of the following clinical characteristics: ≤32 weeks gestation and/or a diagnosis of NEC (≥ Bell’s Stage II). Patients with congenital heart disease (except patent ductus arteriosus), major congenital anomalies, genetic disorders, and inherited blood/metabolic disorders were excluded. A TaqMan allelic discrimination assays were used to determine genotypes Statistical analysis was completed utilizing logistic regression.
Results: Ninety-two African-American infants were recruited for this study, of which 32 had NEC and 9 had spontaneous perforation. Allelic distribution for TNFα, NOS3, and IL1B were in Hardy-Weinberg equilibrium. Utilizing a dominant model, functional variants in TNFα, NOS3, IL1B, IL6, and IL12 were not associated with an increased risk of NEC, NEC totalis, or mortality. A copy of the rare allele for TNFα (rs1800629, -G308A) was associated with an increased risk of spontaneous perforation with an OR 5.97 [95%CI: 1.01 - 35.24, p 0.049].
Conclusions: In premature African-American infants, the functional variations in proinflammatory cytokine genes were not associated with an increased risk of NEC, NEC totalis, or mortality. The TNFα -G308A rare variant was associated with an increased risk of spontaneous perforation.