Cathepsin D is the most abundant lysosomal and endosomal aspartyl protease; it shows beta and gamma secretase activity in vitro by cleaving the amyloid precursor protein into amyloid beta protein. In recent studies, cathepsin D was co-localized with PrP(Sc), the disease-associated form of the prion disease, and abnormal expression of cathepsin D correlated with tissue damage in brains of sporadic Creutzfeldt-Jakob disease (CJD).
To investigate whether a polymorphism at position 224, C224T, on exon 2 of the cathepsin D gene (CTSD) is associated with sporadic CJD in the Korean population.
We compared the genotype and allele frequencies at this polymorphism site in 172 sporadic CJD patients with those in 197 healthy Koreans.
Our study does not show a significant difference in genotype (p = 0.901) and allele (p = 0.509) frequencies of CTSD C224T between sporadic CJD patients and normal controls. This was the first genetic association study of CTSD in a sporadic CJD population.
"CTSD C224T was associated with an increased risk of the development of variant CJD in the British population (86). However, this polymorphism was not associated with an increased risk of sporadic CJD in Korean or European populations (87, 88). "
[Show abstract][Hide abstract] ABSTRACT: Human prion diseases are fatal neurodegenerative disorders that are characterized by spongiform changes, astrogliosis, and the accumulation of an abnormal prion protein (PrPSc). Approximately 10%-15% of human prion diseases are familial variants that are caused by pathogenic mutations in the prion protein gene (PRNP). Point mutations or the insertions of one or more copies of a 24 bp repeat are associated with familial human prion diseases including familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. These mutations vary significantly in frequency between countries. Here, we compare the frequency of PRNP mutations between European countries and East Asians. Associations between single nucleotide polymorphisms (SNPs) of several candidate genes including PRNP and CJD have been reported. The SNP of PRNP at codon 129 has been shown to be associated with sporadic, iatrogenic, and variant CJD. The SNPs of several genes other than PRNP have been showed contradictory results. Case-control studies and genome-wide association studies have also been performed to identify candidate genes correlated with variant and/or sporadic CJD. This review provides a general overview of the genetic mutations and polymorphisms that have been analyzed in association with human prion diseases to date.
Journal of Korean Medical Science 05/2014; 29(5):623-632. DOI:10.3346/jkms.2014.29.5.623 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HECT (homologous to E6-AP carboxyl terminus) E3 ubiquitin ligases are fundamental components of the eukaryotic ubiquitin-proteasome system and are involved in the pathogenesis of several human diseases, including polyglutamine diseases. HECTD2, an E3 ubiquitin ligase, has been linked to the incubation time of prion disease in mice, and its polymorphisms have been associated with sporadic Creutzfeldt-Jakob disease (CJD) in the British population.
To investigate whether 2 HECTD2 polymorphisms, -247G→A (rs7081363) and +16066T→A (rs12249854), are associated with sporadic CJD in the Korean population. Methods: We compared the genotype, allele and haplotype frequencies of the 2 HECTD2 polymorphisms in 205 sporadic CJD patients to those of 208 healthy Koreans.
Our study does not show significant differences in the genotype and allele frequencies of these 2 polymorphisms between sporadic CJD and normal controls. Significant differences in the haplotype frequencies of these 2 polymorphisms were not observed between sporadic CJD and normal controls either. Our results indicate that these 2 HECTD2 polymorphisms are not associated with genetic susceptibility to sporadic CJD in a Korean population. This is the first genetic association study of HECTD2 with sporadic CJD in an Asian population.
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