The First Meta-Analysis of the M129V Single Nucleotide Polymorphism (SNP) of the Prion Protein Gene ( <i>PRNP</i> ) with sporadic Creutzfeldt-Jako disease <i>PRNP</i>) with Sporadic Creutzfeldt-Jakob Disease

Abstract

Background: Prion diseases are fatal, chronic and incurable neurodegenerative diseases caused by pathogenic forms of prion protein (PrPSc) derived from the 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. Methods: 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. Interpretation: We found a very strong association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD using meta-analysis for the first time. We validated the eligibility of existing reports and found severe heterogeneity in some previous studies. We also found the strongest association with the risk of sporadic CJD in the heterozygote comparison model (MM vs. MV, odds ratio = 5.1354, 95% confidence interval: 3.6622; 7.2012, P=0). 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. Funding: This research was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2017R1A6A1A03015876). This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MSIT) (2021R1A2C1013213). Declaration of Interests: The authors declared no conflicts of interest.