Van Everbroeck B, Croes E A, Pals P, Dermaut B, Jansen G, van Duijn C M, Cruts M, Van Broeckhoven C, Martin J J, Cras P
Laboratory of Neurobiology, Born Bunge Foundation, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
Neurosci Lett. 2001 Nov 2;313(1-2):69-72. doi: 10.1016/s0304-3940(01)02264-9.
We investigated the risk associated with the codon 129 polymorphism in the prion protein gene (PRNP) and apolipoprotein E gene (APOE) isoforms for development of Creutzfeldt-Jakob disease (CJD) (n=126) and the possible influences on the disease pathology and its most important clinical characteristics. The PRNP M129V (PRNP129) polymorphism was determined using both DNA extracted from formalin fixed and paraffin embedded brain tissue (n=59) and leukocyte extracted DNA (n=67). In the latter group also the PRNP open reading frame and the APOE genotype were analysed and compared to a neurologically unaffected, age and sex matched control group (n=79). We found that methionine homozygosity of the PRNP129 increases the risk for developing CJD. PRNP129 also influenced the prion accumulation patterns in brain. The APOE 4 allele was an independent risk factor for developing CJD. We further observed a significant dose dependent APOE 4 effect on the number and type of amyloid-beta plaques in the brain of CJD patients.
我们研究了朊蛋白基因（PRNP）密码子129多态性和载脂蛋白E基因（APOE）亚型与克雅氏病（CJD）（n = 126）发生风险的相关性，以及它们对疾病病理及其最重要临床特征的可能影响。使用从福尔马林固定石蜡包埋脑组织中提取的DNA（n = 59）和从白细胞中提取的DNA（n = 67）来确定PRNP M129V（PRNP129）多态性。在后者组中，还分析了PRNP开放阅读框和APOE基因型，并与神经学上未受影响、年龄和性别匹配的对照组（n = 79）进行比较。我们发现PRNP129的甲硫氨酸纯合性会增加患CJD的风险。PRNP129也影响脑中朊病毒的积累模式。APOE 4等位基因是发生CJD的独立危险因素。我们进一步观察到APOE 4对CJD患者脑中淀粉样β斑块的数量和类型有显著的剂量依赖性影响。
