用DHPLC法研究细胞周期蛋白D1的多态性与NPC遗传易感性之间的关系(英文)  

Cyclin D1 Polymorphism and the Susceptibility to NPC Using DHPLC

作　　者：邓琳[1] 赵晓荣[1] 潘凯枫[2] 王祎 邓锡云[1] 吕有勇 曹亚[1] 

机构地区：[1]中南大学湘雅医学院肿瘤研究所分子生物学研究室,长沙410078 [2]北京市肿瘤防治研究所,北京100034

出　　处：《生物化学与生物物理学报》2002年第1期16-20,共5页

基　　金：国家重点基础研究发展规划 ( 973)"恶性肿瘤发生发展的基础研究"(No .G19980 5 12 0 1);国家自然科学基金 (No .30 10 0 0 0 5 );国家自然科学基金杰出青年基金 (No .395 2 5 0 2 2 )资助项目~~

摘　　要：细胞周期蛋白D1是一个关键的细胞周期调节因子和候选的原癌基因 ,其失调参与多种肿瘤 ,包括鼻咽癌的发生。由于细胞周期蛋白D1的基因CCND1第 4外显子存在单个核苷酸多态A/G(A870G) ,因此可产生两种不同的转录本。有报道表明CCND1的基因型与某些肿瘤的临床表型相关。为研究细胞周期蛋白D1的基因型对中国南方散发性鼻咽癌遗传易感性是否存在影响 ,用变性高效液相色谱法 (DHPLC)和DNA测序的方法对 84例鼻咽癌患者和 91例对照的PCR产物进行细胞周期蛋白D1的基因分型。对病例组与对照组基因频率的分布分别进行Hardy Weinberg平衡检验 ,两组间基因频率的差异用 χ2 检验进行比较。结果发现 :在鼻咽癌患者中 ,细胞周期蛋白D1基因型为AA型的 (占 2 0 .2 4% )显著低于正常对照 (占38.46 % ) ,而基因型为GG型和AG型的则显著高于对照 (χ2 =6 .946 ,Pcorrected =0 .0 16 ,OR =2 .46 3,95 %CI =1.2 49～4.85 9)。这表明细胞周期蛋白D1基因的A/G多态性与鼻咽癌的遗传易感性相关 。Cyclin D1 is a key cell cycle regulator and a candidate proto-oncogene, whose deregulation has been implicated in pathogenesis of several types of cancers, including NPC. A common A/G polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G 1/S regulatory protein, and CCND1 genotype has been related to some phenotypes of several tumors. To investigate the influence of cyclin D1 genotypes on the genetic susceptibility in humans from Southern China to sporadic nasopharyngeal carcinoma, cyclin D1 genotyping was performed by denaturing high performance liquid chromatography (DHPLC) and DNA sequencing analysis of the PCR products from 84 NPC cases and 91 normal controls. Gene frequency distribution was tested by Hardy-Weinberg equilibrium and comparison of cyclin D1 gene frequencies between the patient and control groups was performed by χ 2 test. Results showed that in NPC patients, the AA genotype of CCND1 was significantly lower (20.24%) than in normal controls (38.46%), and the GG and AG genotypes (GG + AG) were significantly higher in NPC group than in the control group (χ 2=6.946, Pcorrected=0.016, OR=2.463, 95% CI=1.249—4.859). These suggest that the A/G polymorphism of CCND1 was associated with the susceptibility to NPC, and the GG and AG genotypes in NPC patients were significantly higher than those in normal controls.

关 键 词：细胞周期蛋白D1 多态性 鼻咽癌 变性高效液相色谱法 基因型 易感性 

分 类 号：Q51[生物学—生物化学]