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VEGF Gene Polymorphisms are Associated with Risk of Tetralogy of Fallot

Xiang Li, Chao-Liang Liu, Xiao-Xia Li, Qing-Chen Li, Li-Ming Ma, Gao-Li Liu

Department of Cardiovascular, Affiliated Hospital of Jining Medical University, Jining, Shandong, China (mainland)

Med Sci Monit 2015; 21:3474-3482

DOI: 10.12659/MSM.894568

Available online:

Published: 2015-11-12

BACKGROUND: The aim of this study was to investigate associations of 3 common polymorphisms in the VEGF gene, –2578C>A, –634C>G, and 936C>T, with risk of tetralogy of Fallot (TOF) in Chinese Han children.
MATERIAL AND METHODS: From January 2010 to June 2013, a total of 400 pediatric subjects were recruited, including 160 cases with TOF (TOF group) and 240 healthy controls (control group). The genotypes of 3 common VEGF polymorphisms, –2578C>A, –634C>G, and 936C>T, were analyzed by polymerase chain reaction restriction fragment length polymorphism. All data were analyzed with SPSS 18.0 software.
RESULTS: No significant differences were observed in body mass index or sex between TOF patients and controls (both P>0.05), but significant differences in age and family history of TOF were observed between the 2 groups (both P<0.05). The AA genotype in -2578C>A of VEGF was correlated with a significantly increased risk of TOF, and TOF risk in A allele carrier was 1.54-fold higher than that of C allele carrier (OR=1.54, 95%CI=1.14–2.09, P=0.005); the statistical significance was still present after Bonferroni correction (Pc=0.045). GG genotype in –634C>G of VEGF gene was also associated with an increased risk of TOF, and TOF risk in patients with G allele was 1.62-fold higher compared to patients with C allele (OR=1.62, 95%CI=1.19–2.21, P=0.002); the statistical significance was still present after Bonferroni correction (Pc=0.018). Interestingly, T allele in VEGF 936C>T polymorphism is associated with a decreased TOF risk (OR=0.65, 95%CI=0.49–0.87, P=0.003, the statistical significance was still present after Bonferroni correction (Pc=0.027). The result of logistic regression analysis revealed that –2578C>A, –634C>G, and 936C>T genotypes are independently related to the prevalence of TOF (all P<0.05).
CONCLUSIONS: Our results confirmed that VEGF genetic polymorphisms, –2578C>A and –634C>G, may be associated with an increased TOF risk, while 936C>T polymorphism may be associated with decreased TOF risk.

Keywords: Child, Biomarkers - blood, Alleles, Child, Preschool, China, Echocardiography, Doppler, Gene Frequency, Genotype, Heterozygote, Linkage Disequilibrium, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymorphism, Single Nucleotide, Risk Factors, Software, Tetralogy of Fallot - ultrasonography, Vascular Endothelial Growth Factor A - genetics