Creutzfeldt–Jakob disease risk and<i>PRNP</i>codon 129 polymorphism: necessity to revalue current data

Mitrová, E; Mayer, Vernon W.; Jovankovicová, V; Slivarichova, Dana; Wsólová, Ladislava

doi:10.1111/j.1468-1331.2005.01110.x

Cited by 21 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This putative East-West gradient seems to be confirmed by our analysis. Not only have Japan and Turkey a higher Met-allele prevalence than Denmark, also countries in the Eastern part of Europe like Greece, Finland, Poland and Slovakia [19][20][21][22][23] tend to exhibit a higher occurrence of the Met allele than countries situated in the Western part i.e. France, UK, Iceland, Austria and Denmark [24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

The M129V polymorphism of codon 129 in the prion gene (PRNP) in the Danish population

et al. 2007

View full text Add to dashboard Cite

Since variant Creutzfeldt-Jakob disease (vCJD) was described for the first time in 1995 and fears of an epidemic ensued, the assumed culprit the prion protein (PrP) and its precursor the prion-gene (PRNP) have been subjects to intense studies. Several polymorphisms in PRNP modify disease probability and phenotype. Importantly, two common variants of codon 129 in PRNP code for methionine (Met) or valine (Val), respectively. All hitherto known cases of vCJD have been Met/Met homozygotes. The aim of this study was to investigate the susceptibility to vCJD in the Danish population by determining the distribution of the codon 129 polymorphism. The occurrence of three other relevant polymorphisms were investigated: An alanine (Ala) silent mutation on codon 117, an aspargine-serine (Asn-Ser) mutation on codon 171 and deletions or insertions in the moeity known as the octapeptide region of PRNP. DNA was isolated from 352 samples and alleles were detected by allele specific real-time PCR and/or restriction endonuclease treatment followed by agarose gelelectrophoresis. The distribution of the genotypes at codon 129 was found to be Met/Met 35%, Met/Val 48% and Val/Val 17%. The other polymorphisms were found to be very rare. These data are similar to British data; but differ from the Finnish, Slovakian, Turkish and Japanese distributions, where the Met allele is more abundant. The genetic results indicate that the Danish population is vulnerable to vCJD to the same degree as the British. In Finland, Slovakia, Turkey and Japan the higher frequency of the Met allele may increase the vulnerability to vCJD.

show abstract

Section: Discussionmentioning

confidence: 99%

The M129V polymorphism of codon 129 in the prion gene (PRNP) in the Danish population

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The frequency of the Val-129 allele is ϳ0.3 in Europe, resulting in a frequency of M129V heterozygotes of over 40% (reviewed in Ref. 2). Although the physiological function of PrP, if any, remains obscure, it may be that the maintenance of this polymorphism results from the selective pressure of prion diseases.…”

mentioning

confidence: 99%

Molecular Heterosis of Prion Protein β-Oligomers

Tahiri-Alaoui

Sim

Caughey

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

The gene encoding prion protein is polymorphic in human populations, with over 40% of native Europeans, for example, being heterozygous for the Met-129 and Val-129 alleles. The polymorphism affects both the incidence and the clinical presentation of a range of prion diseases, with heterozygotes generally showing the highest levels of resistance. It has been suggested that an earlier epidemic of prion diseases exerted balancing selection on the two alleles, and we have previously demonstrated that the two encoded proteins have potentially compensating tendencies to form amyloid and soluble ␤-oligomers, respectively, in vitro. More strikingly, here we demonstrate that mixed oligomers, composed of both allelic forms, show an extreme sluggishness in converting to amyloid in comparison with oligomers homogenous for either allele. It may be that this example of molecular heterosis in vitro provides the basis for maintenance of the polymorphism in the population and that ␤-oligomers represent a form of PrP sequestered from pathogenic amyloid formation in vivo.

show abstract

“…Similarly high prevalence of Met/Met but low frequency of Val/Val homozygosity occurred in other Asian populations [18,21,22] (Table 2). In Caucasians, the Val/Val allele was found in about 8-9% population and Met/Val allele in 42-46% subjects [23][24][25][26], with marked significance of difference as compared with Asian (v 2 = 1191.739, df = 2, p < 0.0001). And the distribution of Met/Met homozygosity got more evident in Hans, even compared with the people in the North-Eastern Asia (v 2 = 13.481, df = 2, p = 0.0012).…”

Section: Discussionmentioning

confidence: 84%

Polymorphism distribution of prion protein codon 117, 129 and 171 in Taiwan

Wang

Sun

et al. 2007

Eur J Epidemiol

View full text Add to dashboard Cite

Prion diseases compass transmissible spongiform neurodegenerative diseases from various causes, including the genetic and infectious ones. We investigated the prevalence of codon 117, 129 and 171 polymorphism in prion protein (PrP) in Taiwanese, mainly for the sake of the informative absence of this genetic distribution. Our subjects were 419 aged ones of Han ethic origin. We evaluated the PrP gene (PRNP) polymorphism by restriction fragment length polymorphism, after amplification of their genomic DNAs by polymerase chain reactions with specific primers, digested by restriction enzyme PvuII (for codon 117), NspI (for codon 129), and BbvI (for codon 171), respectively, and confirmed by nucleotide sequencing. All of the subjects were homozygotes at codon 117 (Ala/Ala, gca/gca) and 171 (Asn/Asn, aac/aac). There were no valine homozygotes (Val/Val) in our 419 subjects, and nine subjects (2.1%) showed methionine-valine heterozygosity (Mal/Val, atg/gtg). The methionine homozygotes (Met/Met) comprised the major population (97.9%), and the prevalence of distribution is different to that seen in Caucasians. The almost 100% conservation of the domain from codon 117 to 171 implies the warranty of PrP in cellular functions. The high prevalence of Met/Met alleles in Taiwan did not imply an increased risk of CJD, and the genetic susceptibility of CJD by codon 129 of PrP may be still elusive for the infectivity.

show abstract

Creutzfeldt–Jakob disease risk andPRNPcodon 129 polymorphism: necessity to revalue current data

Cited by 21 publications

References 20 publications

The M129V polymorphism of codon 129 in the prion gene (PRNP) in the Danish population

The M129V polymorphism of codon 129 in the prion gene (PRNP) in the Danish population

Molecular Heterosis of Prion Protein β-Oligomers

Polymorphism distribution of prion protein codon 117, 129 and 171 in Taiwan

Contact Info

Product

Resources

About