一个新硝基还原酶基因NOR1编码区单核苷酸多态及与鼻咽癌的关联分析
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国家重点基础研究发展规划项目(973)(G1998051008),国家高技术“863”计划资助项目(2001AA221031)和国家自然科学基金资助项目(30100027).


Studies of Association Between Nasopharyngeal Carcinoma and Single-Nucleotide Polymorphisms in NOR1, a Novel Oxidored-nitro Domain-containing Protein Gene
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This work was supported by grants from The Special Funds for Major State Basic Research of China (G1998051008), The State 863 High Technology R&D Project of China (2001AA221031) and The National Natural Science Foundation of China (30100027).

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    摘要:

    NOR1基因是中南大学湘雅医学院肿瘤研究所克隆的一个鼻咽癌表达下调新基因,生物信息学预测NOR1基因含有硝基还原酶结构域,该基因可能参与亚硝胺类化学致癌物在体内的代谢过程,从而与鼻咽癌的发生密切相关.通过采用病例-对照的研究方法,利用测序技术对144名鼻咽癌患者和匹配的144名正常人NOR1基因编码区单核苷酸多态(coding region single nucleotide polymorphisms, cSNPs)进行基因分型,关联分析结果显示所检测到的两个cSNPs之间存在连锁不平衡,且均与鼻咽癌发病相关,两个cSNPs及它们所组成的单倍型相对危险度分别为1.36、1.64和1.37.两个cSNPs的多态性改变均使NOR1基因编码蛋白一级结构发生了变化,这种改变可能影响NOR1基因编码蛋白的结构和功能.研究进一步支持了NOR1基因与鼻咽癌的发生发展可能存在密切的关系.

    Abstract:

    Nasopharyngeal carcinoma (NPC) is a rare malignancy tumor in most parts of the world, while with high incidence rate in the south of China. NOR1, a NPC down-regulated gene, was newly-cloned using cDNA micro-array. NOR1 gene has an oxidored-nitro domain predicted by bioinformatics. The latest results suggest that the NOR1 gene may participate in the metabolism of chemical carcinogen such as nitrosamine in vivo. Genotype of coding region single nucleotide polymorphisms (cSNPs) in NOR1 gene were performed by sequencing in 144 unrelated NPC subjects and 144 control subjects which matched in age, sex and residence. Association analysis suggests that there is linkage disequilibrium between the 2 cSNPs, both of them associated with NPC. And the relative risk of 2 cSNPs and their haplotypes were 1.36, 1.64 and 1.37 respectively. Both of the two SNPs could change the sequence of NOR1 protein, which might influence it's structure and function. The results indicated that the SNPs in NOR1 gene may play a certain role in carcinogenesis and development of NPC.

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熊炜,曾朝阳,肖炳燚,熊芳,聂新民,范松青,彭聪,李伟芳,王蓉,沈守荣,李小玲,李桂源.一个新硝基还原酶基因NOR1编码区单核苷酸多态及与鼻咽癌的关联分析[J].生物化学与生物物理进展,2003,30(3):401-405

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  • 收稿日期:2002-11-19
  • 最后修改日期:2003-01-26
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