Association Study Between Of Tie2/Angiopoietin-2and VEGF/KDR Pathway Gene Polymorphisms And Vascular Malformations

BackgroundVascular malformations (VMs) are a common congenital and neonatal dysmorphogenesis.VM can occur in body surface mostly. The lesions can cause functional problems. Extensive lesions can involve an entire limb and cause functional problems. Lesion can affect deep structures and cause airway obstruction.The haplotypes and SNPs can be associated with an increased disease risk. Both Tie2/ANG2and VEGF/VEGFR2receptor-ligand system are involved in normal and pathogenic angiogenesis. VEGFR2and TEM8play a key role in the regulation of VEGF signaling as Tie2in Tie2signaling.ObjectiveIn this study, our aim is to study the association between of Tie2, VEGFR2, Tem8gene polymorphisms and vascular malformations in Chinese Han population.MethodsA total of103Han Chinese patients with vascular malformations and142ethically-matched controls were recuited. DNA was drawn by the peripheral whole blood. We genotyped eight single nucletide polymorphisms in genes of Tie2/ANG2and VEGF/VEGFR2pathway, including rs638203, rs639225, rs80338908and rs80338909in Tie2, rs1870377and rs2305949in VEGFR2, rs79337921and rs34590960in TEM8. The comparison of allele and genotype frequencies of e(?)ch polymorphism between case and control groups was carried out by the software SHEsis. For all statistical analyses, p≤0.05was considered statistically significant.Results1、The frequency of G allele rs638203and allele rs639225of Tie2in VMs is0.495and0.505respectively; And that in control group is0.394and0.396, respectively. The rs638203and allele rs639225was significant associated with VMs. It is predicted that the G allele on two SNPs affect Tie2splicing regulation.2、The frequency of T allele of SNP rs2305949and rs1870377in VMs of VEGFR2is0.210and0.490, respectively; And that in control group is0.165and0.519, respectively. No significant difference was found between VMs and control group.The frequency of A allele of SNP rs79337921and rs34590960in VMs of VEGFR2is0.123and0.882, respectively; and that in control group is0.139and 0.916, respectively. No significant difference was found between VMs and control group.3-. No mutation was found in exon15and exon17of Tie2.4、No significant relation was found between haplotype rs1870377-rs2305949and the risk of VMs. No significant relation was found between haplotype rs34590960-rs79337921and the risk of VMs.ConclusionThe genotype and allele distributions of rs638203and rs639225in Tie2gene differed significantly between VMs patients and controls in Chinese Han population. Further replication studies with larger sample are vital for confirmation of these findings. The exact biological functions and the contribution of Tie2to the VMs are still needed to be clarified.