机构:[1]Hong Kong Univ Sci & Technol, Div Life Sci, Clear Water Bay, Hong Kong, Peoples R China;[2]Hong Kong Univ Sci & Technol, Appl Genom Ctr, Clear Water Bay, Hong Kong, Peoples R China;[3]Capital Med Univ, Dept Neurosurg, Beijing Tiantan Hosp, Beijing, Peoples R China;重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[4]Chinese Univ Hong Kong, Div Neurosurg, Dept Surg, Prince Wales Hosp, Shatin, Hong Kong, Peoples R China;[5]Second Mil Med Univ, Dept Hematol, Inst Hematol, PLA,Changhai Hosp, Shanghai, Peoples R China;[6]Southern Med Univ, Nanfang Hosp, Ctr Canc, Guangzhou, Guangdong, Peoples R China;[7]Univ Hong Kong, Div Neurosurg, Dept Surg, Li Ka Shing Fac Med,Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China;[8]Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Prince Wales Hosp, Shatin, Hong Kong, Peoples R China
ZFPM2, encoding a zinc finger protein and abundantly expressed in the brain, uterus and smooth muscles, plays important roles in cardiac and gonadal development. Abnormal expression of ZFPM2 in ovarian tumors and neuroblastoma has been reported but hitherto its genetic association with cancer and effects on gliomas have not been studied. In the present study, the hexamer insertion-deletion polymorphism rs71305152, located within a large haplotype block spanning intron 1 to intron 3 of ZFPM2, was genotyped in Chinese cohorts of glioma (n = 350), non-glioma cancer (n = 354) and healthy control (n = 463) by direct sequencing and length polymorphism in gel electrophoresis, and ZFPM2 expression in glioma tissues (n = 69) of different grades was quantified by real-time RT-PCR. Moreover, potential natural selection pressure acting on the gene was investigated. Disease-association analysis showed that the overall genotype of rs71305152 was significantly associated with gliomas (P = 0.016), and the heterozygous genotype compared to the combined homozygous genotypes was less frequent in gliomas than in controls (P = 0.005) or non-glioma cancers (P = 0.020). ZFPM2 mRNA expression was negatively correlated with the grades of gliomas (P = 0.002), with higher expression levels in the low-grade gliomas. In the astrocytoma subtype, higher ZFPM2 expression was also correlated with the rs71305152 heterozygous genotype (P = 0.028). In addition, summary statistics tests gave highly positive values, demonstrating that the gene is under the influence of balancing selection. These findings suggest that ZFPM2 is a glioma susceptibility gene, its genotype and expression showing associations with incidence and severity, respectively. Moreover, the balancing selection acting on ZFPM2 may be related to the important roles it has to play in multiple organ development or associated disease etiology.
基金:
University Grants Council of Hong Kong SAR [VPRDO09/10.SC08, VPRDO14SC01, DG14SC02, SRFI11SC06, SRFI11SC06PG]; 863 Program, Ministry of Science and Technology, China [2012AA02A201]
第一作者机构:[1]Hong Kong Univ Sci & Technol, Div Life Sci, Clear Water Bay, Hong Kong, Peoples R China;[2]Hong Kong Univ Sci & Technol, Appl Genom Ctr, Clear Water Bay, Hong Kong, Peoples R China;
通讯作者:
通讯机构:[3]Capital Med Univ, Dept Neurosurg, Beijing Tiantan Hosp, Beijing, Peoples R China;
推荐引用方式(GB/T 7714):
Tsang Shui-Ying,Mei Lingling,Wan Weiqing,et al.Glioma Association and Balancing Selection of ZFPM2[J].PLOS ONE.2015,10(7):-.doi:10.1371/journal.pone.0133003.
APA:
Tsang, Shui-Ying,Mei, Lingling,Wan, Weiqing,Li, Jun,Li, Yi...&Xue, Hong.(2015).Glioma Association and Balancing Selection of ZFPM2.PLOS ONE,10,(7)
MLA:
Tsang, Shui-Ying,et al."Glioma Association and Balancing Selection of ZFPM2".PLOS ONE 10..7(2015):-