title: HIF-1α genetic variants and protein expression confer the susceptibility and prognosis of gliomas.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yi
authors.forename: Xuwei
authors.initials: X
authors.lastname: Hou
authors.forename: Ji
authors.initials: J
authors.lastname: Zhou
authors.forename: Lunshan
authors.initials: L
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Ouyang
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.forename: Zhaocong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Hongjie
authors.initials: H
authors.lastname: Chen
authors.forename: Minhui
authors.initials: M
authors.lastname: Xu
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D002681:China / Q000453:epidemiology; D005260:Female; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000502:physiology; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000494:pharmacology; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering