Association between mannose-binding lectin gene polymorphisms and necrotizing enterocolitis in preterm infants

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-2YA/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 >400ng/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.