Rasheed Urwah, Khalid Minahil, Noor Aneeqa, Saeed Umar, Uppal Rizwan, Zafar Saima
Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology, Islamabad, Pakistan.
Department of Research and Development, Islamabad Diagnostic Center (IDC), Islamabad, Pakistan.
Prion. 2024 Dec;18(1):1-7. doi: 10.1080/19336896.2024.2439598. Epub 2024 Dec 9.
Rapidly progressive dementias (RPDs) are a type of fatal dementias that cause rapid progression of neuronal dysfunction. This study aimed to assess the prevalence of APOE genotypes (ε2, ε3, ε4) and PRNP mutations (E200K, M129V) in the general population of Pakistan because of their association with RPDs, including Rapidly Progressive Alzheimer's Disease (rpAD) and Creutzfeldt-Jakob Disease (CJD). Blood samples ( = 100) were collected from healthy Pakistani population and the stated mutations were assessed using polymerase chain reaction. In the analysis of the APOE genotype, ε3/ε3 genotype was the most common (95%), followed by ε3/ε4 (5%) and ε2 allele was completely absent. A low frequency of ε4 allele and the absence of a protective ε2 allele is associated with an increased risk of rpAD. In the case of PRNP mutations, the most common genotype was M129-Ε200 (71%) and V129-Ε200 (29%). E200K mutation was completely absent from the given population. It is noteworthy that the MM homozygous genotype was present in 71 samples, VV genotype was present in 29. Homozygosity on codon 129, as observed in most of our samples, has been associated with more efficient production of PrP and disease pathology. This study provides preliminary data indicating that rpAD and CJD pose a significant threat to the Pakistani population.
快速进展性痴呆（RPDs）是一类致命性痴呆，可导致神经元功能快速进展。本研究旨在评估巴基斯坦普通人群中APOE基因型（ε2、ε3、ε4）和PRNP突变（E200K、M129V）的患病率，因为它们与RPDs相关，包括快速进展性阿尔茨海默病（rpAD）和克雅氏病（CJD）。从健康的巴基斯坦人群中采集了血液样本（n = 100），并使用聚合酶链反应评估所述突变。在APOE基因型分析中，ε3/ε3基因型最为常见（95%），其次是ε3/ε4（5%），ε2等位基因完全缺失。ε4等位基因频率较低且缺乏保护性ε2等位基因与rpAD风险增加相关。在PRNP突变方面，最常见的基因型是M129 - Ε200（71%）和V129 - Ε200（29%）。给定人群中完全不存在E200K突变。值得注意的是，71个样本中存在MM纯合基因型，29个样本中存在VV基因型。正如我们大多数样本中所观察到的，密码子129处的纯合性与PrP的更有效产生和疾病病理学相关。本研究提供的初步数据表明，rpAD和CJD对巴基斯坦人群构成重大威胁。
