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Genetic Variants of VEGF (rs201963 and rs3025039) and KDR (rs7667298, rs2305948, and rs1870377) Are Associated with Glioma Risk in a Han Chinese Population: a Case-Control Study

Abstract

A glioma is the most common type of brain tumor that accounts for nearly 80 % of brain cancers. Vascular endothelial growth factor (VEGF) and its receptor, the kinase insert domain receptor (KDR), are involved in the angiogenesis of cancers. In this study, we investigate whether the polymorphisms of VEGF and KDR are associated with a glioma risk. Blood samples were collected from 477 glioma patients and 477 healthy controls. Five tag-single nucleotide polymorphisms (SNPs) of KDR were obtained from the HapMap database, and eight tag-SNPs of VEGF were selected based on previous studies. After extraction of genomic DNAs by a Qiagen DNA blood kit, the SNPs of VEGF and KDR were genotyped with a Sequenom MassArray iPLEX platform and further analyzed with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. The odds ratios and their 95 % confidence interval (95 % CI) were used to assess the association between VEGF, KDR polymorphisms, and glioma risks with the aid of SPSS 13.0 software. The haplotype analysis demonstrated that two SNPs of VEGF [rs3025039 (C>T), rs2010963 (G>C)] could elevate the susceptibility to a glioma in the homozygous model [odds ratio (OR) = 3.13 (95 % confidence interval (CI) 1.30–7.49, P = 0.007) and OR = 1.58 (95 % CI 1.07–2.34, P = 0.022), respectively], dominant model [OR = 1.38 (95 % CI 1.04–1.84, P = 0.025) and OR = 1.32 (95 % CI 1.01–1.72, P = 0.043), respectively], and allelic model [OR = 1.43 (95 % CI 1.11–1.84, P = 0.005) and OR = 1.24 (95 % CI 1.04–1.50, P = 0.019), respectively]. Furthermore, three SNPs of KDR [rs7667298 (A>G), rs2305948 (C>T), rs1870377 (T>A)] were also assumed to be associated with an increased risk of a glioma in the homozygous [OR = 1.93 (95 % CI 1.30–2.86, P = 0.001), OR = 2.56 (95 % CI 1.28–5.11, P = 0.006), and OR = 1.52 (95 % CI 1.00–2.31, P = 0.049), respectively], dominant [OR = 1.52 (95 % CI 1.16–1.98, P = 0.002), OR = 1.41 (95 % CI 1.05–1.87, P = 0.020), and OR = 1.48 (95 % CI 1.13–1.93, P = 0.004), respectively], and allele models [OR = 1.39 (95 % CI 1.15–1.67, P = 0.001), OR = 1.47 (95 % CI 1.14–1.89, P = 0.002), and OR = 1.27 (95 % CI 1.05–1.52, P = 0.013), respectively]. The genetic polymorphisms of VEGF [rs3025039 (C>T), rs2010963 (G>C)] and KDR [rs7667298 (A>G), rs2305948 (C>T), rs1870377 (T>A)] increased glioma susceptibility in a Chinese population, suggesting the possibility of VEGF and KDR as genetic markers for glioma. Additional functional and association studies with different ethnic groups included are needed to further confirm our results.

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Acknowledgments

This work was supported by grants from the National Nature Science Foundation (81372705), the Shanghai Science and Technology Development Fund (10JC1409802), and the Wu Jieping Medical Foundation (320.6750.11092).

Conflict of Interest

The authors declare that they have no competing interests.

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Correspondence to Jie Chen or Jianwei Ge.

Additional information

Jiannan Zhang, Jian Yang, and Yuqing Chen equally contributed to this work.

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Zhang, J., Yang, J., Chen, Y. et al. Genetic Variants of VEGF (rs201963 and rs3025039) and KDR (rs7667298, rs2305948, and rs1870377) Are Associated with Glioma Risk in a Han Chinese Population: a Case-Control Study. Mol Neurobiol 53, 2610–2618 (2016). https://doi.org/10.1007/s12035-015-9240-0

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Keywords

  • Glioma
  • Vascular endothelial growth factor
  • Kinase insert domain receptor
  • Single nucleotide polymorphism
  • Han Chinese population
  • Genetic markers