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

<b><i>Background:</i></b> 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. <b><i>Objective:</i></b> To study whether common polymorphisms of the genes encoding VEGF-A and VEGFR-2 are associated with BPD. <b><i>Methods:</i></b> In this association study, six tagging single nucleotide polymorphism (tSNPs) for <i>VEGFA</i> and 25 tSNPs for <i>VEGFR2</i> 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. <b><i>Results:</i></b><i>VEGFR2</i> 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. <b><i>Conclusions:</i></b> 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 <i>VEGFA</i> and <i>VEGFR2</i> 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.