Lack of Association betweenPRNPM129V Polymorphism and Multiple Sclerosis, Mild Cognitive Impairment, Alcoholism and Schizophrenia in a Korean Population

Abstract

Abstract.The genetic variant at codon 129 (M129V) of the prion protein gene (PRNP) is considered to be a major genetic risk factor for prion diseases. In this study, we examined the possible genetic association of PRNP*129Val with multiple sclerosis (MS, n = 681), mild cognitive impairment (MCI, n = 801), alcoholism (n = 761) and schizophrenia (n = 715) in a Korean population, and compared the data with previous genetic association studies of the variant. The minor allele frequency of PRNP*129Val (MAF = 0.025) was significantly lower in Korean population (n = 2,479) compared to Caucasian populations (P < 0.0001), suggestive of a weak influence of the variant in the previous population. Statistical analysis revealed no significant association between PRNP*129Val and MS (P = 0.76), MCI (P = 0.46), alcoholism (P = 0.84) and schizophrenia (P = 0.69). These findings were discussed in the context of prior inconsistent reports on the role of PRNP*129Val polymorphism in several diseases. Results from this study may provide further evidence that PRNP M129V is not a genetic susceptibility factor for MS, MCI, alcoholism and schizophrenia in a Korean population.

Prion protein codon 129 polymorphism in mild cognitive impairment and dementia: the Rotterdam Study

“…Another potential limitation is the generalizability of our findings, as our study was performed in mainly Caucasians. Previous studies have studied the effect of the M129V polymorphism of the PRNP gene in mild cognitive impairment and different types of dementia in Asians ( Jeong et al , 2007 ; Choi et al , 2010 ; Zhang et al , 2016 ). No association was found between the M129V polymorphism and mild cognitive impairment in a Korean population ( Choi et al , 2010 ).…”

“…While the dementia seen in Creutzfeldt–Jakob disease patients is likely a result of prion protein aggregation, various studies suggest that the PRNP gene is also involved in other forms of dementia, but results are inconsistent ( Rujescu et al , 2003 ; Del Bo et al , 2006 ; Jeong et al , 2007 ; Poleggi et al , 2008 ; Choi et al , 2010 ; Golanska et al , 2013 ; He et al., 2013 ; Zhang et al , 2016 ). Furthermore, studies performed on early cognitive decline and early-ons et Al zheimer’s disease also show inconsistency regarding which of the homozygous carriers have a higher risk ( Croes et al , 2003 ; Dermaut et al , 2003 ).…”

Alzheimer's Disease and Prion Protein

“…Another function is that PrP C physically interacts with the APP cleaving enzyme BACE1 through its N-terminal polybasic domain (residues 23-26) and inhibits its enzyme activity, resulting in a reduction of Aβ production (74)(75)(76), which indicates a preventive role against AD. In both cell and animal models, PrP C has been shown to lower Aβ production by inhibiting BACE1 (75,76).This function is thought to be modulated by PRNP polymorphism at codon 129 (M129V), which may be associated with increased risk of AD (77)(78)(79)(80)(81). Interestingly, binding of Aβ oligomers to PrP C impairs the inhibitory effect of PrP C on BACE1 activity (64), which may indicate another mechanism of Aβ oligomer toxicity.…”

The prion protein M129V polymorphism

“…15,16 However, not all studies find associations. [17][18][19][20] These reported studies concern middle-aged individuals or elderly persons at most in their 80s or 90s, not the oldest-old, centenarians, who have selectively survived, avoided, fatal conditions. In this paper we present the first genetic association study of the PRNP codon 129 polymorphism among Polish centenarians (n = 150) comparing genotypic frequencies to those found for a sample of younger Poles aged 18 to 56 years (n = 165).…”