原发进行性失语患者的朊蛋白密码子129基因型患病率改变  

Prion protein codon 129 genotype preva-lence is altered in primary progressive aphasia

作　　者：Rowland L.P Mitsumoto H J.A. Mastrianni 邱伟庆 

机构地区：[1]Department of Neurology, MC 2030, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, United States,Dr.

出　　处：《世界核心医学期刊文摘（神经病学分册）》2006年第5期16-17,共2页Digest of the World Core Medical Journals:Clinical Neurology

摘　　要：The prion protein (PrP) is central to the prion diseases, although a role in other neurodegenerative diseases has been postulated. A common polymorphism (Met or Val) at codon 129 of the PrP gene (PRNP) features prominently in the risk and phenotype, of prion disease, and an abnormality in its distribution frequency may signal a role for PrP in other diseases. We conducted a case-control study to compare the PRNP codon 129 genotype distribution in Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and primary progressive aphasia (PPA), including 281 AD, 256 ALS,39 PPA, and 415 healthy control subjects. Statistical analysis was applied to determine the presence or absence of disease-specific genotype associations. The distribution of codon 129 genotypes was similar among healthy control, AD, and ALS subjects, although the heterozygous state was significantly overrepresented (age-adjusted odds ratio, 8.47) in PPA, a rare condition of unknown cause.Although these findings do not entirely exclude a role for PrP in AD or ALS, they do not support the codon 129 genotype as a risk factor for either disease. However, the strong association between heterozygosity and PPA raises new questions about its cause and the role of PrP in other neurodegenerative diseases.The prion protein （PrP） is central to the prion diseases, although a role in other neurodegenerative diseases has been postulated. A common polymorphism （Met or Val） at codon 129 of the PrP gene （PRNP） features prominently in the risk and phenotype, of prion disease, and an abnormality in its distribution frequency may signal a role for PrP in other diseases. We conducted a case-control study to compare the PRNP codon 129 genotype distribution in Alzheimer＇s disease （AD）, amyotrophic lateral sclerosis （ALS）, and primary progressive aphasia （PPA）, including 281 AD, 256 ALS,39 PPA, and 415 healthy control subjects. Statistical analysis was applied to determine the presence or absence of disease-specific genotype associations. The distribution of codon 129 genotypes was similar among healthy control, AD, and ALS subjects, although the heterozygous state was significantly overrepresented （age-adjusted odds ratio, 8. 47） in PPA, a rare condition of unknown cause. Although these findings do not entirely exclude a role for PrP in AD or ALS, they do not support the codon 129 genotype as a risk factor for either disease. However, the strong association between heterozygosity and PPA raises new questions about its cause and the role of PrP in other neurodegenerative diseases.

关 键 词：原发进行性失语 基因型分布 失语患者 朊蛋白病 密码子 肌萎缩侧索硬化(ALS) 患病率 病例对照研究 PrP基因 神经变性疾病 

分 类 号：R767.64[医药卫生—耳鼻咽喉科] R512.62[医药卫生—临床医学]