Genotype patterns and characteristics of PRNP in the Korean population
Genotype patterns and characteristics of PRNP in the Korean population
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DOI：
10.4161/pri.20195
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发表时间：
2012-09-01
期刊：
影响因子：
2.3
通讯作者：
Kim, Su Yeon
中科院分区：
文献类型：
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作者：
Lee, Sol Moe;Ju, Young Ran;Kim, Su Yeon
克雅氏病(CJD)是人类可传播的海绵状脑病(TSE)中的一种疾病，众所周知是由错误折叠的Prion蛋白在大脑中异常堆积引起的。人PrNP基因定位于染色体20p13，发现了许多单核苷酸多态性(SNPs)。然而，PRNP中的SNPs的功能尚不清楚，尽管已有几个SNPs被认为是与人类PrP疾病易感性有关的重要突变。我们的目的是确定PRNP基因组区域的特定基因型模式和特征，并了解韩国歧视的普恩病患者、疑似CJD患者和KARE数据组的易感性。在这里，我们研究了韩国鉴别的普恩病毒病患者组(n=22)、疑似普恩病毒病患者组(n=163)和韩国协会资源数据库(KARE)数据库组(n=296)的PRNP的基因分型和SNPs等位基因频率。在481份样本中，测序区域分别为启动子区域、外显子1和外显子2及其连接部分。本研究共发现了25个SNPs。除rs2756271外，所有SNPs的核苷酸频率都非常倾向于显性纯合型。密码子129和219编码区的基因频率与以前在韩国和日本的研究结果相似。鉴别CJD患者组出现102P/L、200E/K、203V/I等致病突变，疑似Prion病患者组和KARE资料组出现180V/I、232M/R等致病突变。共发现10个SNP，其中6个位于启动子区域，1个位于外显子2，3个位于3‘非编码区。位于密码子219编码区的rs57633656和rs1800014之间存在着强烈且独特的连锁不平衡(D‘=0.94，r(2)=0.89)。我们期望提供这些数据，以确定不仅在韩国人，而且在东亚人中，普恩病毒疾病的特定易感性和保护性因素。
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.