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
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
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VEGF（rs201963 和 rs3025039）和 KDR（rs7667298、rs2305948 和 rs1870377）的遗传变异与中国汉族人群的胶质瘤风险相关：一项病例对照研究
DOI：
10.1007/s12035-015-9240-0
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发表时间：
2016-05
影响因子：
5.1
通讯作者：
Ge Jianwei
中科院分区：
文献类型：
--
作者：
Zhang Jiannan;Yang Jian;Chen Yuqing;Mao Qin;Li Shanquan;Xiong Wenhao;Lin Yingying;Chen Jie;Ge Jianwei
神经胶质瘤是最常见的脑肿瘤，占脑癌的近80%。血管内皮生长因子（VEGF）及其受体激酶插入结构域受体（KDR）参与肿瘤血管生成。在这项研究中，我们研究了VEGF和KDR的多态性是否与胶质瘤风险相关。研究人员采集了477名神经胶质瘤患者和477名健康对照者的血液样本。从HapMap数据库中获得KDR的5个标签单核苷酸多态性（snp），并根据前人的研究筛选出VEGF的8个标签snp。通过Qiagen DNA blood试剂盒提取基因组DNA后，使用Sequenom MassArray iPLEX平台对VEGF和KDR的snp进行基因分型，并进一步使用基质辅助激光解吸电离飞行时间（MALDI-TOF）质谱法进行分析。使用比值比及其95%置信区间（95% CI），借助SPSS 13.0软件评估VEGF、KDR多态性与胶质瘤风险之间的关系。单体型分析表明,两个snp VEGF (rs3025039 (C> T) rs2010963 (G> C)]可以提升对神经胶质瘤的纯合模型(优势比(或)= 3.13(95%可信区间(CI) 1.30 - -7.49, P = 0.007)或= 1.58 (95% CI 1.07 - -2.34, P = 0.022),分别),占主导地位的模型(或= 1.38 (95% CI 1.04 - -1.84, P = 0.025)或= 1.32 (95% CI 1.01 - -1.72, P = 0.043),分别),和等位基因模型(或= 1.43 (95% CI 1.11 - -1.84,P = 0.005),或= 1.24 (95% CI 1.04 - -1.50, P = 0.019),分别)。此外,三个单核苷酸多态性KDR [rs7667298 (A> G), rs2305948 (C> T) rs1870377 (T>)也被认为是与神经胶质瘤的风险增加有关纯合子(或= 1.93 (95% CI 1.30 - -2.86, P = 0.001),或= 2.56 (95% CI 1.28 - -5.11, P = 0.006),或= 1.52 (95% CI 1.00 - -2.31, P = 0.049),分别),主导(或= 1.52 (95% CI 1.16 - -1.98, P = 0.002),或= 1.41 (95% CI 1.05 - -1.87, P = 0.020),或= 1.48 (95% CI 1.13 - -1.93, P = 0.004),分别),和等位基因模型(或= 1.39 (95% CI 1.15 - -1.67, P = 0.001),或= 1.47 (95% CI 1.14 - -1.89, P = 0.002),或= 1.27 (95% CI 1.05 - -1.52, P = 0.013),分别)。VEGF基因多态性[rs3025039 (C>；T), rs2010963 (G>；C)]和KDR基因多态性[rs7667298 (A>；G), rs2305948 (C>；T), rs1870377 (T>；A)]在中国人群中增加胶质瘤易感性，提示VEGF和KDR可能作为胶质瘤的遗传标记。为了进一步证实我们的结果，还需要对不同族群进行额外的功能和关联研究。
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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影响因子：
30.8
作者：
Shete S;Hosking FJ;Robertson LB;Dobbins SE;Sanson M;Malmer B;Simon M;Marie Y;Boisselier B;Delattre JY;Hoang-Xuan K;El Hallani S;Idbaih A;Zelenika D;Andersson U;Henriksson R;Bergenheim AT;Feychting M;Lönn S;Ahlbom A;Schramm J;Linnebank M;Hemminki K;Kumar R;Hepworth SJ;Price A;Armstrong G;Liu Y;Gu X;Yu R;Lau C;Schoemaker M;Muir K;Swerdlow A;Lathrop M;Bondy M;Houlston RS
通讯作者：
Houlston RS
影响因子：
24
作者：
Wang, Yibo;Zheng, Yi;Hui, Rutal
通讯作者：
Hui, Rutal
影响因子：
9.8
作者：
Nagy, Janice A.;Benjamin, Laura;Zeng, Huiyan;Dvorak, Ann M.;Dvorak, Harold F.
通讯作者：
Dvorak, Harold F.
DOI：
--
发表时间：
2003-08
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Yi-Hong Zhou;Fang Tan;K. Hess;W. Yung
通讯作者：
Yi-Hong Zhou;Fang Tan;K. Hess;W. Yung
影响因子：
4.3
作者：
Knizetova, Petra;Ehrmann, Jiri;Bartek, Jiri
通讯作者：
Bartek, Jiri