Supplementary Material for: Genes Encoding Vascular Endothelial Growth Factor A (VEGF-A) and VEGF Receptor 2 (VEGFR-2) and Risk for Bronchopulmonary Dysplasia

Background: Bronchopulmonary dysplasia (BPD) is one of the main consequences of prematurity, with notably high heritability. Vascular endothelial growth factor A (VEGF-A) and its main receptor, vascular endothelial growth factor receptor 2 (VEGFR-2), have been implicated in the pathogenesis of BPD. Objective: To study whether common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are associated with BPD. Methods: In this association study, six tagging single nucleotide polymorphism (tSNPs) for VEGFA and 25 tSNPs for VEGFR2 were genotyped in a prospectively collected, genetically homogeneous discovery population of 160 infants (44 infants with grade 2-3 BPD) born before 30 completed gestational weeks. The replication population of 328 infants included 120 cases of BPD. Results:VEGFR2 SNP rs4576072 was associated with BPD grade 2-3 with a minor allele frequency in 23.9% of the cases compared to 9.1% in controls (p = 0.0005, odds ratio 3.15, 95% CI: 1.62-6.12) in the discovery population. This association was not observed in the more heterogeneous replication population. Conclusions: In line with the results of recent large-scale genetic studies, our findings indicate that common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are not consistently associated with BPD. This finding does not rule out the involvement of VEGFA and VEGFR2 in BPD pathogenesis since, in addition to common variations within the gene region, other mechanisms also play important roles in the regulation of gene function.