阿尔茨海默病患者环氧化酶-2基因启动子区多态性分析  

A study of COX-2 polymorphisms in patients with Alzheimer’s disease

作　　者：任美峰[1] 黄绍宽 沙松华 成林平[2] 范海虹[4] 程冠杰 汪华侨[1] 

机构地区：[1]中山大学中山医学院解剖学教研室脑研究室,广东广州510080 [2]广州市老人院 [3]深圳市社会福利中心康复医院,深圳市518049 [4]中山大学附属第一医院

出　　处：《解剖学研究》2009年第1期9-13,共5页Anatomy Research

基　　金：国家重点基础研究发展计划(973计划)(2006cb500700);广东省科技计划项目(2006B36030003;2008B030301320);广东省医学科学技术研究基金(A2006181)

摘　　要：目的检测环氧化酶-2(COX-2)基因的1195和765两个多态位点,探讨其与阿尔茨海默病(AD)的可能相关性。方法采用Qiagen DNA提取试剂盒提取外周血白细胞DNA,根据位点基因序列设计引物,采用PCR-限制性片段长度多态分析(PCR-RFLP)分别对90例AD患者(AD组)和110例正常人(对照组)进行基因分型,PCR扩增出各样本的目的片断,对扩增产物进行酶切,酶切产物经2%琼脂糖凝胶电泳,EB染色,凝胶成像系统判定结果。结果AD组共检出3种COX-2-1195基因型,GG基因型频率为21.0%,GA基因型频率为50.0%,AA基因型频率为29.0%,G、A等位基因频率分别为46.1%和53.9%,与对照组比较,差异均无统计学意义;GG基因型频率为77.8%,GC基因型频率为20.0%,CC基因型频率为2.2%,G、C等位基因频率分别为87.8%和12.2%,与对照组比较,AD组中CC基因型频率、C等位基因频率差异均有统计学意义。COX-2蛋白水平在AD组和对照组分别为(124.95±8.73)IU/L、(51.81±7.33)IU/L,差异有统计学意义(P<0.05)。结论①COX-2基因启动子区-1195G/A多态性可能与中国南方人群AD的发生无关;②COX-2基因～765G/C与AD的发生有关,-765G/C多态性可能是AD发生的一风险因素;③AD患者血浆中COX-2蛋白水平升高,可能是由于COX-2基因-765G/C多态性引起。Objective To examine the two variants （-1195G/A and -765G/C in the promoter） of COX-2, and explore its correlation with Alzheimer＇s disease risk. Methods The genomic DNA of 110 cases without AD diseases control group, 90 patients with AD group was extracted by using Qiagen DNA Extraction KIT. Genotypes of COX-2-1195 and COX-2-765 of all groups were determined by polymerase chain reaction-based restriction fragment length polymorphism （PCR-RFLP）. Results （1） Compared with controls, -1195 G/A genotype and the frequency of the mutant A allele in AD has no statistic significance. （2） -765G/C genotype frequencies and the frequency of the mutant C allele in AD has statistic significance compared with controls, and CC genotype and the frequency of mutant C allele in AD was higher in controls. （3）The COX-2 level in serum of AD patients was higher than controls. Conclusions （1） The -l195G/A gene mutation may not represent a genetic risk factor for AD patients. （2） The -765G/C gene mutation may associated with AD. The -765G/C polyphysim may represent a genetic risk factor for AD patients. （3）The -765G/C polymorphisms in the regulatory regions of the COX-2 gene may result in higher COX-2 level in serum of AD patients.

关 键 词：阿尔茨海默病 环氧化酶-2 基因型 单核苷酸多态性 限制性片段长度多态性 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R562.25[医药卫生—临床医学]