Affiliations: [a] Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
| [b] Institute for Genomic Medicine Clinical Laboratory, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
| [c] Center for Cardiovascular and Pulmonary Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
| [d] Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH, USA
Correspondence:
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Address for correspondence: Jennifer K. Trittmann, Center for Perinatal Research, Abigail Wexner Research Institute, Nationwide Children’s Hospital; 575 Children’s Crossroads, Research Building III, Sixth Floor, Columbus, OH 43215 Phone (614) 355 6623; Fax (614) 355 5896 E-mail: [email protected].
Abstract: BACKGROUND:Differences in the susceptibility of preterm infants to develop necrotizing enterocolitis (NEC) implicate potential genetic differences in response to the inflammatory stimuli leading to NEC. Dual specificity phosphatases (DUSPs) are a key suppressor pathway of the mitogen-activated protein kinase (MAPK) pro-inflammatory signaling pathway. We hypothesized that inherited single nucleotide polymorphisms (SNPs) in DUSP genes contribute to NEC susceptibility in premature infants. METHODS:Patients admitted between 2010 and 2015 born at < 32 weeks GA and≤1,500 g BW with stage II+NEC (cases; n = 50) and age, weight-matched controls (n = 38) were included. Blood samples were collected for DNA isolation. Agena Mass Array assay was used to examine 31 SNPs in 9 different DUSP genes. Calculated minor allele frequencies (MAF) for cases and controls were compared using χ2 and logistic regression. RESULTS:The presence of the rs704074 SNP was associated with a 48% decreased risk of developing NEC (OR 0.52; 95% CI 0.27– 1.01, p = 0.04). The odds of surgical NEC decreased by 78% (OR 0.22; 95% CI 0.06– 0.84, p = 0.027) for each copy of rs704074/G allele in patients with NEC. CONCLUSION:In this small single-center pilot study, DUSP-6 SNP (rs704074) was associated with a lower risk of developing NEC and surgical NEC, the most severe form of NEC, in preterm infants.
