The First Meta-Analysis of the M129V Single-Nucleotide Polymorphism (SNP) of the Prion Protein Gene (PRNP) with Sporadic Creutzfeldt-Jakob Disease.

Yong-Chan Kim,Byung-Hoon Jeong

doi:10.3390/cells10113132

Abstract

Prion diseases are fatal, chronic, and incurable neurodegenerative diseases caused by pathogenic forms of prion protein (PrPSc) derived from endogenous forms of prion protein (PrPC). Several case–control and genome-wide association studies have reported that the M129V polymorphism of the human prion protein gene (PRNP) 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 PRNP 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 PRNP gene and susceptibility to sporadic CJD. We found a very strong association between the M129V SNP of the PRNP 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, p < 1 × 10−10). To the best of our knowledge, this was the first meta-analysis assessment of the relationship between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD.

Highlights

Prion diseases are chronic, lethal, and malignant neurodegenerative diseases caused by toxic forms of prion protein (PrPSc ) derived from benign prion protein (PrPC ), which is encoded by the prion protein gene (PRNP) [1,2,3,4,5]
To identify an association between the M129V single-nucleotide polymorphism (SNP) of the PRNP gene and susceptibility to sporadic Creutzfeldt–Jakob disease (CJD), we performed an association analysis between sporadic CJD patients and matched control populations, including Caucasian and East Asian populations obtained from the 1000 Genomes Project
We evaluated the association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD using a meta-analysis

Summary

Introduction

Lethal, and malignant neurodegenerative diseases caused by toxic forms of prion protein (PrPSc ) derived from benign prion protein (PrPC ), which is encoded by the prion protein gene (PRNP) [1,2,3,4,5]. Prion diseases are classified into three types: sporadic, genetic, and acquired. The most common type of human prion disease is sporadic Creutzfeldt–Jakob disease (CJD), which accounts for approximately. Genetic forms of human prion disease, accounting for 10–15% of all CJD cases, occur due to germline mutations of the PRNP gene. These forms include fatal familial insomnia (FFI) with the D178N-129M genotype; Gerstmann–Sträussler–Scheinker syndrome (GSS) with P102L, A117V, and F198S mutations; and genetic CJD, including the G114V, D178N-129V, V180I, E200K, and V210I mutations. Acquired forms of human prion disease account for less than 1% of all CJD cases, including iatrogenic CJD, kuru, and variant CJD, which are caused by consuming meat from bovine spongiform encephalopathy (BSE)-affected cattle [6,7,8,9,10]. The cause of sporadic CJD has not been elucidated far

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