Yi Liang, Hou Xuwei, Zhou Ji, Xu Lunshan, Ouyang Qing, Liang Hong, Zheng Zhaocong, Chen Hongjie, Xu Minhui
Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Neuromolecular Med. 2014 Sep;16(3):578-86. doi: 10.1007/s12017-014-8310-1. Epub 2014 Jun 15.
To investigate the role of HIF-1α genetic polymorphism of c.1772C>T and c.1790G>A in the incidence and prognosis of gliomas in a Chinese cohort, a total of 387 gliomas patients and 437 age- and sex-matched healthy controls were recruited. The genetic polymorphism of c.1772C>T and c.1790G>A was determined. We found that the genotype distribution at c.1772C>T showed significant difference between patients and controls. Multivariable analyses showed a significantly higher risk for gliomas in 1772TT genotype carriers (odds ratio 2.68, with CC as reference). In addition, we also found a significantly higher risk for grade III + IV gliomas was observed in 1772TT genotype carriers (odds ratio 2.21, with CC as reference). The overall survival rates in patients with 1772TT or 1772CT genotype were markedly lower compared with patients with CC (both P < 0.01). Our in vitro studies revealed that HIF-1α regulates the proliferation, migration and invasion of human glioma U251 cells. This study suggests that the c.1772C>T polymorphisms may be used as a molecular marker for gliomas occurrence, grades and clinical outcome in gliomas patients.
为了研究c.1772C>T和c.1790G>A的HIF-1α基因多态性在中国人群胶质瘤发病及预后中的作用，我们招募了387例胶质瘤患者和437例年龄及性别匹配的健康对照。测定了c.1772C>T和c.1790G>A的基因多态性。我们发现c.1772C>T位点的基因型分布在患者和对照之间存在显著差异。多变量分析显示，1772TT基因型携带者患胶质瘤的风险显著更高（优势比2.68，以CC为参照）。此外，我们还发现1772TT基因型携带者发生III + IV级胶质瘤的风险显著更高（优势比2.21，以CC为参照）。1772TT或1772CT基因型患者的总生存率显著低于CC基因型患者（均P < 0.01）。我们的体外研究表明，HIF-1α调节人胶质瘤U251细胞的增殖、迁移和侵袭。本研究提示，c.1772C>T多态性可能作为胶质瘤患者胶质瘤发生、分级及临床结局的分子标志物。
