Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Korea.
Department of Bioactive Material Sciences, Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Korea.
Cells. 2021 Nov 11;10(11):3132. doi: 10.3390/cells10113132.
Prion diseases are fatal, chronic, and incurable neurodegenerative diseases caused by pathogenic forms of prion protein (PrP) derived from endogenous forms of prion protein (PrP). Several case-control and genome-wide association studies have reported that the M129V polymorphism of the human prion protein gene () is significantly associated with susceptibility to sporadic Creutzfeldt-Jakob disease (CJD). However, since some case-control studies have not shown these associations, the results remain controversial. We collected data that contain the genotype and allele frequencies of the M129V single-nucleotide polymorphism (SNP) of the gene and information on ethnic backgrounds from sporadic CJD patients. We performed a meta-analysis by collecting data from eligible studies to evaluate the association between the M129V SNP of the gene and susceptibility to sporadic CJD. We found a very strong association between the M129V SNP of the gene and susceptibility to sporadic CJD using a meta-analysis for the first time. We validated the eligibility of existing reports and found severe heterogeneity in some previous studies. We also found that the MM homozygote is a potent risk factor for sporadic CJD compared to the MV heterozygote in the heterozygote comparison model (MM vs. MV, odds ratio = 4.9611, 95% confidence interval: 3.4785; 7.0758, < 1 × 10). To the best of our knowledge, this was the first meta-analysis assessment of the relationship between the M129V SNP of the gene and susceptibility to sporadic CJD.
朊病毒病是由朊病毒蛋白（PrP）的致病性形式引起的致命性、慢性和不可治愈的神经退行性疾病，这些致病性形式源自朊病毒蛋白（PrP）的内源性形式。几项病例对照和全基因组关联研究报告称，人类朊病毒蛋白基因（）中的 M129V 多态性与散发性克雅氏病（CJD）的易感性显著相关。然而，由于一些病例对照研究并未显示出这些关联，因此结果仍存在争议。我们收集了包含散发性 CJD 患者基因中 M129V 单核苷酸多态性（SNP）的基因型和等位基因频率以及种族背景信息的数据。我们通过收集合格研究的数据进行了荟萃分析，以评估基因中 M129V SNP 与散发性 CJD 易感性之间的关联。我们首次通过荟萃分析发现基因中 M129V SNP 与散发性 CJD 易感性之间存在很强的关联。我们验证了现有报告的资格，并发现一些先前研究存在严重的异质性。我们还发现，与 MV 杂合子相比，MM 纯合子是散发性 CJD 的一个强有力的危险因素，在杂合子比较模型中（MM 与 MV，比值比=4.9611，95%置信区间：3.4785；7.0758，<1×10）。据我们所知，这是首次对基因中 M129V SNP 与散发性 CJD 易感性之间关系的荟萃分析评估。
