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学科主题: 基础医学
题名:
Two single-nucleotide polymorphisms with linkage disequilibrium in the human programmed cell death 5 gene 5 ′ regulatory region affect promoter activity and the susceptibility of chronic myelogenous leukemia in Chinese population
作者: Ma, X; Ruan, GR; Wang, Y; Li, QY; Zhu, P; Qin, YZ; Li, JL; Liu, YR; Ma, DL; Zhao, HS
刊名: CLINICAL CANCER RESEARCH
发表日期: 2005-12-15
DOI: 10.1158/1078-0432.CCR-05-0039
卷: 11, 期:24, 页:8592-8599
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: CHRONIC MYELOID-LEUKEMIA ; COLONY-STIMULATING FACTOR ; BCR-ABL ; CELL-DEATH ; APOPTOSIS ; CHEMOTHERAPY ; BINDING ; CANCER ; TRANSCRIPTION ; METASTASIS
英文摘要:

Purpose: Chronic myelogenous leukemia (CML) is a disease characterized cytogenetically by the presence of the Philadelphia chromosome. Recent studies suggested that altered PDCD5 expression may have significant implications in CML progression. The aim of this study was to identify single- nucleotide polymorphisms (SNP) within the programmed cell death 5 (PDCD5) promoter region and show their functional relevance to PDCD5 expression as well as their genetic susceptibility to CML.

Experimental Design: One hundred twenty-nine CML subjects and 211 healthy controls were recruited for identification of SNPs and subsequent genetic analysis. Luciferase reporter assays were carried out to show the functional significance of the SNPs located in the promoter region to PDCD5 expression. Real-time quantitative PCR and Western blot analysis were done to determine the expression differences of PDCD5 in CIVIL patients with different genotypes.

Results: Two SNPs were identified within the PDCD5 promoter. They are -27A > G and -11G > A (transcription start site as position, 1), respectively. The complete linkage disequilibrium was found between these two polymorphisms. The frequencies of -27G(+)/-11A(+) genotype and -27G/-11A allele were significantly higher in CML patients than in healthy controls (genotype: 26.36% versus 11.85%, chi(2)=11.75, P < 0.01; allele: 13.57% versus 6.40%, chi(2) = 9.48, P < 0.01). Luciferase reporter assays revealed that the promoter with -27G/-11A had significantly lower transcriptional activity and could not be up-regulated after apoptotic stimulations compared with the promoter with -27A/-11G. PDCD5 expression analysis in mononuclear cells derived from CML patients and cell lines with different -27/-11 genotypes showed consistent results with the reporter assays.

Conclusions: These data suggest that -27G/-11A is associated with reduced PDCD5 promoter activity and increased susceptibility to CML.

语种: 英语
WOS记录号: WOS:000234356300011
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58178
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Peking Univ, Dept Prosthodont, Beijing 100871, Peoples R China
2.Peking Univ, Beijing, Peoples R China
3.Peking Univ, Dept Immunol, Sch Basic Med, Ctr Human Dis Genom, Beijing 100083, Peoples R China
4.Peking Univ, Dept Periodontol, Sch Stomatol, Beijing 100871, Peoples R China
5.Peking Univ, Peoples Hosp, Inst Hematol, Beijing 100871, Peoples R China
6.Peking Univ, Hosp 1, Dept Hematol, Beijing 100871, Peoples R China

Recommended Citation:
Ma, X,Ruan, GR,Wang, Y,et al. Two single-nucleotide polymorphisms with linkage disequilibrium in the human programmed cell death 5 gene 5 ′ regulatory region affect promoter activity and the susceptibility of chronic myelogenous leukemia in Chinese population[J]. CLINICAL CANCER RESEARCH,2005,11(24):8592-8599.
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