title: Glioma Association and Balancing Selection of ZFPM2.
abstract: 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.
authors.affiliation: Division of Life Science and Applied Genomics Centre, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Shui-Ying
authors.initials: SY
authors.lastname: Tsang
authors.affiliation: Division of Life Science and Applied Genomics Centre, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wan
authors.affiliation: Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Life Science and Applied Genomics Centre, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Cunyou
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Division of Life Science and Applied Genomics Centre, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Ding
authors.affiliation: Division of Life Science and Applied Genomics Centre, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Pun
authors.affiliation: Department of Hematology, Institute of Hematology, PLA, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Hematology, Institute of Hematology, PLA, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cancer Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
authors.affiliation: Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Siu-Tim
authors.initials: ST
authors.lastname: Cheung
authors.affiliation: Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: Gilberto K K
authors.initials: GK
authors.lastname: Leung
authors.affiliation: Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Wai-Sang
authors.initials: WS
authors.lastname: Poon
authors.affiliation: Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Life Science and Applied Genomics Centre, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation; D007438:Introns / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D009369:Neoplasms / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012641:Selection, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; C117427:ZFPM2 protein, human