Abstract
A polymorphism (M129V) at codon 129 of the prion protein gene (PRNP) results in either a methionine residue (Met) or a valine residue (Val) and is known to determine susceptibility for the development of sporadic or acquired Creutzfeldt-Jakob disease (CJD). The distributions of M129V genotypes and alleles in various general populations have been reported and there are clear differences between Western Europeans and East Asians. We analysed the coding sequence of the PRNP gene in 100 healthy Turkish subjects to determine whether the distributions of the M129V genotypes and alleles or other PRNP gene variants in the Turkish population differ from those in other normal populations. Three known polymorphisms but no other gene variants were detected in the PRNP coding sequence of the Turkish individuals. Genotype frequencies at codon 129 were 57% Met/Met, 34% Met/Val and 9% Val/Val, with an allele frequency of 0.740 : 0.260 Met:Val. These distributions are considerably different from those reported for other normal populations residing in Western Europe and East Asia, except in Crete. The higher frequency of 129 Met-homozygotes in Turkey than in Western Europe suggests that the Turkish are at greater risk of developing CJD.
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Prusiner SB . Shattuck lecture–neurodegenerative diseases and prions N Engl J Med 2001 344: 1516–1526
Palmer MS, Dryden AJ, Hughes JT, Collinge J . Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease [published erratum appears in Nature 1991; 352: 547] Nature 1991 352: 340–342
Laplanche JL, Delasnerie-Lauprêtre N, Brandel JP et al. Molecular genetics of prion diseases in France Neurology 1994 44: 2347–2351
Salvatore M, Genuardi M, Petraroli R, Masullo C, D'Alessandro M, Pocchiari M . Polymorphisms of the prion protein gene in Italian patients with Creutzfeldt-Jakob disease [published erratum appears in Hum Genet 1995; 95: 605] Hum Genet 1994 94: 375–379
Alpérovitch A, Zerr I, Pocchiari M et al. Codon 129 prion protein genotype and sporadic Creutzfeldt-Jakob disease [published erratum appears in Lancet 2000; 355: 72] Lancet 1999 353: 1673–1674 Letter
Collinge J, Palmer MS, Dryden AJ . Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease Lancet 1991 337: 1441–1442
Zeidler M, Ironside JW . The new variant of Creutzfeldt-Jakob disease Rev Sci Tech 2000 19: 98–120
Doh-ura K, Kitamoto T, Sakaki Y, Tateishi J . CJD discrepancy Nature 1991 353: 801–802
Tsai MT, Su YC, Chen YH, Chen CH . Lack of evidence to support the association of the human prion gene with schizophrenia Mol Psychiatry 2001 6: 74–78
Peoc'h K, Manivet P, Beaudry P et al. Identification of three novel mutations (E196K, V203I, E211Q) in the prion protein gene PRNP in inherited prion diseases with Creutzfeldt-Jakob disease phenotype Hum Mutat 2000 15: 482
Palmer MS, van Leeven RH, Mahal SP, Campbell TA, Humphreys CB, Collinge J . Sequence variation in intron of prion protein gene, crucial for complete diagnostic strategies Hum Mutat 1996 7: 280–281 Letter
Laplanche JL, Chatelain J, Launay JM, Gazengel C, Vidaud M . Deletion in prion protein gene in a Moroccan family Nucleic Acids Res 1990 18: 6745
Yamada M, Itoh Y, Fujigasaki H et al. Deletion in the prion protein gene in a Japanese family Biomed Res (Tokyo) 1994 15: 131–133
Palmer MS, Mahal SP, Campbell TA et al. Deletions in the prion protein gene are not associated with CJD Hum Mol Genet 1993 2: 541–544
Doh-ura K, Tateishi J, Sasaki H, Kitamoto T, Sakaki Y . Pro→leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Straussler syndrome Biochem Biophys Res Commun 1989 163: 974–979
Deslys JP, Marcé D, Dormont D . Similar genetic susceptibility in iatrogenic and sporadic Creutzfeldt-Jakob disease J Gen Virol 1994 75: 23–27
Combarros O, Sanchez-Guerra M, Llorca J et al. Polymorphism at codon 129 of the prion protein gene is not associated with sporadic AD Neurology 2000 55: 593–595
Zimmermann K, Turecek PL, Schwarz HP . Genotyping of the prion protein gene at codon 129 Acta Neuropathol (Berl) 1999 97: 355–358
Plaitakis A, Viskadouraki AK, Tzagournissakis et al. Increased incidence of sporadic Creutzfeldt-Jakob disease on the island of Crete associated with a high rate of PRNP 129-methionine homozygosity in the local population Ann Neurol 2001 50: 227–233
Cavalli-Sforza L, Menozzi P, Piazza A . The history and geography of human genes Princeton: Princeton University Press 1994 pp205–254
Deslys JP, Jaegly A, d'Aignaux JH, Mouthon F, Billette de Villemeur T, Dormont D . Genotype at codon 129 and susceptibility to Creutzfeldt-Jakob disease Lancet 1998 351: 1251 Letter
Acknowledgements
This study was held on behalf of the Prion Diseases Study Group in Turkey and supported by the Scientific and Technical Research Council of Turkey (TUBITAK, grant no: 196S104/SBAG-1666) and by the Turkish Psychiatry Association. We thank Martine Lenne for excellent technical assistance.
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Erginel-Unaltuna, N., Peoc'h, K., Komurcu, E. et al. Distribution of the M129V polymorphism of the prion protein gene in a Turkish population suggests a high risk for Creutzfeldt-Jakob disease. Eur J Hum Genet 9, 965–968 (2001). https://doi.org/10.1038/sj.ejhg.5200754
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DOI: https://doi.org/10.1038/sj.ejhg.5200754
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