Absence of Association between Codon 129 and 219 Polymorphisms of the Prion Protein Gene and Vascular Dementia

Abstract

Background: Polymorphisms of the prion protein gene (PRNP) are known to cause a strong susceptibility to the occurrence of prion diseases, such as Creutzfeldt-Jakob disease, and might be associated with other neurodegenerative disorders. However, an association between PRNP polymorphisms and vascular dementia (VaD) has not been reported thus far. Objective: To investigate whether the PRNP polymorphisms are associated with an increased risk for developing VaD in the Korean population. Methods: We compared the genotype, allele and haplotype frequencies of PRNP polymorphisms in 160 VaD patients with those in 236 healthy Koreans. Results and Conclusion: Codon 129 (M129V) and 219 (Q219K) polymorphisms in Korean VaD patients were found in the open reading frame of PRNP. Our study shows that there is no significant difference in the genotype, allele and haplotype frequencies of PRNP codon 129 and 219 polymorphisms between Korean VaD patients and normal controls. This was the first genetic association study of the polymorphisms of PRNP with VaD.

PRNP 1368 polymorphism is not associated with sporadic Creutzfeldt‐Jakob disease in the Korean population

“…In our previous studies, we found that polymorphisms within the coding region of PRNP are not associated with sporadic Alzheimer’s disease or vascular dementia (VaD) [33,34]. The downstream prion‐like protein (doppel) encoded by prion‐like protein gene ( PRND ) shares structural homology with the prion protein.…”

Genetic polymorphism in exon 2 of cathepsin D is not associated with vascular dementia

“…Associations between VaD and polymorphisms of candidate genes have been investigated, including hemostatic genes, genes controlling homocystein, lipid metabolism genes, the angiotensin‐converting enzyme gene, and the endothelial nitric oxide synthase gene (6). In our previous studies, we found that in the Korean population, codons 129 and 219 polymorphisms within the ORF of PRNP and the polymorphism ( PRNP 1368) upstream of PRNP exon 1 did not correlate with the development of VaD (35–37).…”

Lack of association between PRNP 1368 polymorphism and Alzheimer's disease or vascular dementia

“…This controversial result may be due to the different sample size of the population analyzed, to a difference in frequency of PRNP genotypes between different ethnic groups [ 29 ], or even to a difference in age of onset. In our previous studies, we failed to detect a significant association between PRNP polymorphism at codons 129/219 and the risk for AD or VaD in the Korean population [ 30 , 31 ].…”