Association of VEGFA polymorphisms with necrotizing enterocolitis in Chinese Han population

Abstract

Our results suggested that, if validated in larger studies, screening for VEGFA SNPs and plasma levels might be useful as a risk factor for NEC in the future.

Risk of Necrotizing Enterocolitis Associated With the Single Nucleotide Polymorphisms VEGF C-2578A, IL-18 C-607A, and IL-4 Receptor α-Chain A-1902G: A Validation Study in a Prospective Multicenter Cohort

“…Differences in the inclusion criteria and the ethnic background of the studied populations may account for these different results. The study of Banyasz et al included infants with all stages of NEC (12), whereas our study and the study of Gao et al (13) only included infants with confirmed NEC (Bell stage II disease or greater). As highlighted by Cuna et al, (31).…”

“…As mentioned in the introduction, two previous studies showed that the A allele of the VEGF C-2578A SNP increased the risk of NEC in preterm infants (12,13). Moreover, one of the studies showed that plasma VEGFA levels were significantly lower in carriers of the A allele (13).…”

“…VEGF is an angiogenic protein that couples hypoxia sensing to angiogenesis and is necessary for the development and maintenance of capillary networks (9). It is suggested that VEGF-mediated alterations of the intestinal mucosal microvasculature play an important role in NEC pathogenesis (9,13,24,25). In fact, intestinal VEGF protein expression is reduced in human and experimental NEC (9,26).…”

“…However, few of these genetic studies have been replicated in validation cohorts (3). In the present study we aimed to confirm the association with NEC of three candidate SNPs: the VEGF C-2578A polymorphism (rs699947) (12,13), the IL-18 C-607A polymorphism (rs1946518) (14), and the IL-4 receptor αchain (IL-4Rα) A-1902G polymorphism (rs1801275) (15). We performed our investigation in a cohort of preterm infants from four neonatal intensive care units located in three different European countries (Spain, Italy, and the Netherlands) (16,17).…”

Advances in our understanding of the molecular pathogenesis of necrotizing enterocolitis

“…Investigation of a large group of preterm newborns (358 cases with 26 cases of NEC ≥ stage II) for the association of SNPs with risk of NEC in VEGF C-2578A (rs699947), IL-18 C-607A (rs1946518), and IL-4Rα (IL-4 receptor α-chain) A-1902G (rs1801275) revealed that all three SNPs were not significantly different from infants with or without NEC under various genetic models, but the G-allele of the IL-4Rα A-1902G SNP was significantly negative association with the outcome NEC or death [ 51 ]. Using the SEQUENOM Mass Array platform assay, data from 30 NEC patients and 80 controls in Chinese Han population indicated that the VEGFA SNPs rs699947 and rs833061 were low in plasma and are associated with high risk of NEC [ 52 ]. Investigation of 751 patients with extremely low birth weight (30 had surgical NEC) using genome-wide association study tool PLINK for the link between genetic variations and increased risk of surgical NEC (stage III) revealed that 261 SNPs are allelic differences in NEC vs. no NEC, 35 of that are significantly different.…”