The c.1039 G>A single nucleotide polymorphisms in VEGFA gene are associated with the increased risk for bicuspid aortic valve

Objective:To determine the role of vascular endothelial growth factor A (VEGFA) gene variation in the development of bicuspid aortic valve (BAV).Methods:A total of 74 unrelated pediatric patients with BAV were enrolled.Blood samples were collected from BAV patients and 300 healthy controls.All eight coding exons and exon-intron boundaries of the VEGFA gene were amplified and sequenced.Pedigree investigation was carried out by transthoracic echocardiography and corresponding sequence analysis in the patients who were confirmed to have a gene variation.Results:A heterozygous single nucleotide polymorphism (SNP) c.1039 G>A in exon 6 and a homozygous SNP c.1039 G>A in exon 6,which were not previously reported,were identified in two and one patient,respectively.These polymorphisms changed the protein sequence,replacing a valine by an isoleucine at residue 347 (p.Val347Ile) of the VEGFA protein.VEGFA 1039A allele frequency was more prevalent in BAV subjects than in controls (2.70% vs 0.33%,P<0.05).Having VEGFA 1039A allele presented increased risk for BAV (odds ratio 8.306,95% CI 1.507-45.788).For two heterozygous BAV patients,the G-to-A transition at cDNA position 1039 was transmitted from mothers.For homozygous BAV patients,8 family members were heterozygous carrier;2 family members were diagnosed as dilated aortic root,of which one was heterozygous carrier.Conclusions:The c.1039 G>A SNPs in the VEGFA may be associated with the increased risk for BAV.The dilated aortic root and BAV may share a common developmental risk factor.