BRD7单核苷酸多态性及鼻咽癌易感性分析
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国家863项目(102-10-01-05)、973重点项目《“疾病基因组学”理论和技术体系的建立》及国家自然科学基金(39700158,30000065)资助.


Coding-region Single Nucleotide Polymorphisms in BRD7 Gene and Nasopharyngeal Carcinoma Susceptiblity
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This work was supported by grants from the National High Technology “863”Program of China(102-10-01-05); “973”Key Research Programs of China and the National Natural Sciences Foundation of China(39700158 and 30000065).

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    摘要:

    为了探讨BRD7基因的遗传变异在鼻咽癌发生的作用,采用PCR-SSCP和直接测序方法对BRD7 基因的编码区进行单核苷酸多态性(coding-region single nucleotide polymorphism, cSNP)分析,并对两个鼻咽癌家系的高危成员、57个散发性鼻咽癌病人和50个正常人进行了BRD7等位基因分型.在BRD7基因的编码区发现了3个cSNP(C450T、A538C和A737G),其中A538C颠换导致其编码蛋白的第162个氨基酸由Asp变为Ala;C450T改变与同义的A737C多态性偶联发生在87.7%的鼻咽癌活检组织和配对的外周血、所有的鼻咽癌家系的患者及8个易感成员,但是仅存在于22%的正常人血标本中.C450T多态性变化可以导致其编码蛋白在第133位氨基酸的翻译终止(G133Ter).以上结果说明,C450T和A737C偶联的多态性改变是鼻咽癌发生和发展的重要遗传易感风险因子之一(P<0.01);BRD7基因有两种翻译方式,G133Ter可以导致另一种截断的翻译本(truncated isoform).

    Abstract:

    In order to evaluate the role of inherited variation in the BRD7 gene in human nasoparyngeal carcinoma. RT-PCR, SSCP and sequencing were used to identified multiple coding-region single nucleotide polymorphisms (cSNPs), three cSNPs in BRD7 were found in fifty-seven sporadic biopsy specimens and corresponding blood samples from the same NPC patients and two pedigrees of NPC family. One of those cSNPs is A538C transition, which creates a missense change of Asp162Ala in three of NPC patients analyzed and three of fifty healthy individuals. Adjacent to the bromodomain (504~609 nt), another SNP (C450T) behind the start condon (484nt) results in a G133Ter substitution in 87.7% NPC biopsies and corresponding blood samples, all affected family members in the pedigrees and eight of nine susceptible members, the third SNP is synonymous polymorphism (A737G) which is coupled interestingly with the C450T alteration. The latter two forms of SNPs are also observed in eleven of fifty control normal blood samples. This findings suggest that the presence of the two coupled SNPs in BRD7 might be one of important risk factors for the development and/or progression of NPC (P<0.01), and the BRD7 gene might have two modes of translation and the terminational SNP at 450 nt in BRD7 gene results in the second alternatively truncated isoform.

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余鹰,朱诗国,向娟娟,李忠花,张必成,曹利,李桂源. BRD7单核苷酸多态性及鼻咽癌易感性分析[J].生物化学与生物物理进展,2001,28(4):568-572

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  • 收稿日期:2001-03-07
  • 最后修改日期:2001-04-05
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