Genotype patterns and characteristics of PRNP in the Korean population

Abstract

Creutzfeldt-Jakob disease (CJD), included in the human transmissible spongiform encephalopathies (TSE), is widely known to be caused by an abnormal accumulation of misfolding prion protein in the brain. Human prion protein gene (PRNP) is mapped in chromosome 20p13 and many single nucleotide polymorphisms (SNPs) in PRNP have been discovered. However, the functionality of SNPs in PRNP is yet unclear, though several SNPs have been known as important mutation related with susceptibility human prion diseases. Our aim is to identify specific genotype patterns and characteristics in the PRNP genomic region and to understand susceptibility among Korean discriminated prion disease patients, suspected CJD patients and the KARE data group. Here, we have researched genotypes and SNPs allele frequencies in PRNP in discriminated prion disease patients group (n = 22), suspected prion diseases patients group (n = 163) and the Korea Association REsource (KARE) data group (n = 296) in Korea. The sequencing regions were promoter region, exon1 and exon2 with their junction parts among 481 samples. A total of 25 SNPs were shown in this study. Nucleotide frequencies of all SNPs are exceedingly tended to bias toward dominant homozygote types except in rs2756271. Genotype frequencies at codon 129 and 219 coding region were similar with previous studies in Korea and Japan. Pathogenic mutations such as 102P/L, 200E/K and 203V/I were observed in discriminated CJD patients group, and 180V/I and 232M/R were shown in suspected prion disease patients group and the KARE data group. A total of 10 SNPs were newly identified, six in the promoter region, one in exon 2 and three in the 3' UTR. The strong and unique linkage disequilibrium (D' = 0.94, r (2) = 0.89) was observed between rs57633656 and rs1800014 which is located in codon 219 coding region. We expect that these data can be provided to determine specific susceptibility and a protective factor of prion diseases not only in Koreans but also in East Asians.

Analysis of 12 Chinese Patients with Proline-to-Leucine Mutation at Codon 102-Associated Gerstmann-Sträussler-Scheinker Disease

“…The polymorphism at PRNP codon 219 with the substitution of glutamate for lysine seems to be found only in Asian population, and not in Caucasians 2627. P102L GSS patients with this polymorphism have been described as showing different clinical and pathological features 27282930. The lysine at codon 219 is believed to be protective against sCJD.…”

<p>Early-onset Alzheimer’s disease patient with prion <em>(PRNP)</em> p.Val180Ile mutation</p>

“…Nevertheless, several previous reports support the hypothesis that PRNP mutation is not always associated with a prion disease. According to the genotype analysis of PRNP in a South Korean population, including prion disease patients group (n=22), suspected prion diseases patient group (n=163) and Korea Association Resource (KARE) data group, three cases of Val180Ile mutations were reported, and two cases from the KARE data group did not display characteristics or symptoms of the neurodegenerative disorder 16. Prion diseases may share some features such as dementia phenotype and pathological characteristics with AD.…”

Rare V180I mutation in PRNP gene of a Chinese patient with Creutzfeldt-Jakob disease

“…However, this mutation is recognized as the most common cause of fCJD in Japan. 10,11,12 Although 2 individuals with V180I from Korea Association Resource (KARE) do not display symptoms of neurodegenerative disorder and V180I heterozygosity is considered not pathogenic factors but rarely observed polymorphisms, 13 the World Health Organization has listed CJD180 as familial CJD. 14 The case described in this study is the first V180I gCJD in China since the surveillance for human prion diseases began in 2006.…”