Objectives: The aim of the present study was to evaluate whether polymorphisms of the mannose-binding lectin (MBL-2) gene and MBL serum levels on admission to neonatal intensive care unit are associated with necrotizing enterocolitis (NEC) in preterm infants and to verify MBL expression in NEC bowels.
Methods: In this retrospective cohort study, 107 neonates (41 with NEC and 66 controls) were included. MBL-2 genotyping for the promoter polymorphism −221 and for the exon 1 variant alleles at codons 52, 54, and 57 was performed. MBL levels were determined by enzyme-linked immunosorbent assay in 55 infants. Immunohistochemical staining for MBL expression was performed on bowel specimens. The main study outcome was severe NEC (Bell stages II/III).
Results: The −221 Y allele and the MBL-2 YY genotype were more frequent in neonates with severe NEC than in controls (P = 0.04 and P = 0.004, respectively). In the multivariate analysis, the MBL-2 YA/YA genotype was associated with NEC (odds ratio = 3.03, 95% confidence interval 1.13%–8.13%, P = 0.024). Neonates with NEC had MBL level on admission >400 ng/mL more frequently than controls (P = 0.043). Among neonates with severe NEC, the deceased neonates were carriers of high or intermediate producing MBL-2 genotypes (P = 0.035). Finally, MBL was highly expressed in intestinal tissue from infants with NEC.
Conclusions: MBL-2 genotypes associated with high MBL serum levels represent a risk factor for NEC. This finding, together with the MBL expression in bowel tissue, supports a role for MBL in the pathogenesis of NEC.
*Laboratory of Rheumatology, Bambino Gesù Children's Hospital, Rome
†Department of Pediatrics, Anna Meyer Children's University Hospital, Firenze
‡Division of Pathology
§Clinical Chemistry Laboratory
¶Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, Rome, Italy.
Address correspondence and reprint requests to Cinzia Auriti, MD, Department of Neonatology, Neonatal Intensive Care Unit, Bambino Gesù Children's Hospital, 00165 Piazza S. Onofrio 4, 00165 Rome, Italy (e-mail: email@example.com).
Received 29 September, 2011
Accepted 2 February, 2012
The study was supported by the Health Department of the Italian Government (Italian Ministry of Health: Grant 200602P/001751) and by Bambino Gesù Children's Hospital.
The authors report no conflicts of interest.