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 regionsinglenucleotidepolymorphism ,cSNP)分析 ,并对两个鼻咽癌家系的高危成员、 5 7个散发性鼻咽癌病人和 5 0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 (C45 0T、A5 38C和A737G) ,其中A5 38C颠换导致其编码蛋白的第 16 2个氨基酸由Asp变为Ala ;C45 0T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 2 2 %的正常人血标本中 .C45 0T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 ,C45 0T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 0 1) ;BRD7基因有两种翻译方式 ,G133Ter可以导致另一种截断的翻译本 (truncatedisoform) .
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.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2001年第4期568-572,共5页
Progress In Biochemistry and Biophysics
基金
国家 8 63项目 (10 2 10 0 1 0 5 )
973重点项目<"疾病基因组学"理论和技术体系的建立>
国家自然科学基金(3 970 0 15 8
3 0 0 0 0 0 65 )资助~~
关键词
鼻咽肿瘤
BRD7基因
易感基因
单核苷酸多态性
nasopharyngeal neoplasms, BRD7 gene, susceptiblity gene, single nucleotide polymorphisms
