title: The M129V polymorphism of codon 129 in the prion gene (PRNP) in the Danish population.
abstract: 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.
authors.affiliation: Laboratory of Neuropathology, 6301 Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Dyrbye
authors.forename: Helle
authors.initials: H
authors.lastname: Broholm
authors.forename: Morten Hanefeld
authors.initials: MH
authors.lastname: Dziegiel
authors.forename: Henning
authors.initials: H
authors.lastname: Laursen
mesh_terms: D000328:Adult; D000368:Aged; D000409:Alanine / Q000235:genetics; D000483:Alleles; D003062:Codon / Q000235:genetics*; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D003718:Denmark; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D012694:Serine / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D012694:Serine; D014633:Valine; D000409:Alanine