Endocardial cushion defects (ECDs) of the cardiac outflow tract are among the most common
congenital heart disease phenotypes.
VEGF is essential for endocardial cushion formation and derangements in
VEGF synthesis lead to ECD. Three functional single nucleotide polymorphisms (SNPs) in the
VEGF gene -2578 C>A, -1154 G>A, and -634 G>C play a role in cardiogenesis. In a Dutch case-control family study of triads, 190 case and 317 control children with both parents, we investigated linkage and association between these
VEGF SNPs and ECD. Allele frequencies for the three
VEGF SNPs were comparable between ECD children and controls. However,
VEGF alleles -2578 C and -1154 G were transmitted more frequently to children with ECD (p = 0.003 and p = 0.002), in particular perimembranous
ventricular septal defects (p = 0.012 and p = 0.006). The -2578A/-1154A/-634G haplotype was associated with a reduced risk of ECD (OR 0.7; 95% CI, 0.6-1.0) and was significantly less transmitted to children with ECD (p = 0.002). In a Dutch population, we show that the
VEGF 2578 C, -1154 G alleles, and the AAG haplotype are associated with ECD. Possible
VEGF gene-environment interactions exposures are discussed.
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