Genetic polymorphisms of toll-like receptor 4 in very low birth weight infants with necrotizing enterocolitis

Background: Necrotizing enterocolitis (NEC) is a life-threatening disorder of the immature neonates, affecting up to 10 percent of patients treated at neonatal intensive centers. While its pathophysiology is still unclear, data emphasize the importance of disturbed innate immunity, of which Toll-like receptor 4 (TLR4) is a central component. Two common functional mutations (SNP) of TLR4 gene (A+896G, C+1196T) have been recently described and been linked to a change of Asp to Gly at site 299 and Thr to Ile at site 399, respectively. Data suggest that these mutations are associated with altered TLR4 function. Objectives: In our study we investigated the prevalence and association of TLR4 genotype with the risk of NEC.

Methods: TLR4 genotype was analysed by PCR and RFLP methods in 133 very low birth weight (b.w. <1500 grams) infants (VLBW). Genotyping for Asp299Gly and Thr399Ile SNPs was successful for 127 and 119 infants, respectively. Of those, 51 suffered in NEC. The prevalence of the investigated SNPs was compared to that in 146 and 138 healthy newborns with normal birth weight.

Results: We found similar prevalence of Asp299Gly SNP either in VLBW or in healthy newborns (0.07 vs. 0.04, NS). The prevalence of Thr399Ile SNP was lower in VLBW than in healthy neonates (0.08 vs. 0.04, p=0.04). However, prevalence of TLR4 genotypes was similar in patients with or without NEC.

Conclusion: These findings do not support that Asp299Gly and Thr399Ile SNPs would associate with NEC. However, there may be a link between Thr399Ile alleles and premature birth, which is the primary risk factor of this severe neonatal complication.