Russian Journal of Genetics

, Volume 45, Issue 5, pp 605–612 | Cite as

Polymorphism of the prion protein gene PRNP and risk of multiple sclerosis development in ethnic Russians from Bashkortostan

  • O. V. Chubukova
  • O. E. Mustafina
  • A. V. Chemeris
  • I. A. Tuktarova
  • K. Z. Bahtijarova
  • R. V. Magjanov
  • Yu. M. Nikonorov
Human Genetics


M129V polymorphism of prion protein gene PRNP has been studied in patients with multiple sclerosis (MS) and healthy ethnic Russians from Bashkortostan using allele-specific PCR. The genotype frequency distribution of the examined polymorphism in Russians from Bashkortostan was similar to that in European populations. MM, MV, and VV genotype frequencies in control group and in the MS patients were 50.24%, 42.58%, 7.18% and 43.33%, 45.83%, 10.84%, respectively. It was shown that in the group of MS patients with onset of the disease at the age of 21 and older, the frequency of the VV genotype was higher than in the control group (14.3% versus 6.18%, respectively, P = 0.041). We suggest that the VV genotype is associated with higher risk factor of MS development in the patients aged 21 years and older.


Multiple Sclerosis Multiple Sclerosis Patient Prion Protein Prion Disease PRNP Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Zuev, V.A., From Prion Diseases to the Problem of Aging and Death, Vestn. Ross. Akad. Med. Nauk, 2001, no. 11, pp. 46–49.Google Scholar
  2. 2.
    Tahiri-Alaoui, A., Gill, G., Disterer, P., and James, W., Methionine 129 Variant of Human Prion Protein Oligomerizes More Rapidly than Valine 129 Variant, J. Biol. Chem., 2004, vol. 279, pp. 31390–31397.PubMedCrossRefGoogle Scholar
  3. 3.
    Pruisiner, S., Prions, Proc. Natl. Acad. Sci. USA, 1998, vol. 95, pp. 13363–13383.CrossRefGoogle Scholar
  4. 4.
    Inge-Vechtomov, S.G., Yeast Prions and the Central Dogma of Molecular Biology, Vestn. Ross. Akad. Nauk, 2000, vol. 70, no. 4, pp. 299–306.Google Scholar
  5. 5.
    Lee, I., Westaway, D., Smit, A., et al., Complete Genomic Sequence and Analysis of the Prion Protein Gene Region from Three Mammalian Species, Genome Res., 1998, vol. 8, pp. 1022–1037.PubMedGoogle Scholar
  6. 6.
    Alperovich, A., Zerr, I., Pocchiari M., et al., Codon 129 Prion Protein Genotype and Sporadic Creutzfeldt-Jakob Disease, Lancet, 1999, vol. 353, pp. 1673–1674.CrossRefGoogle Scholar
  7. 7.
    Palmer, M.S., Dryden, A.J., Hughes, J.T., and Collinge, J., Homozygous Prion Protein Genotype Predisposes to Sporadic Creutzfeldt-Jakob Disease, Nature, 1991, vol. 352, pp. 340–342.PubMedCrossRefGoogle Scholar
  8. 8.
    Croes, E.A., Alizadeh, B.Z., Bertoli-Avella, A.M., et al., Polymorphisms in the Prion Protein Gene and in the Doppel Gene Increase Susceptibility for Creutzfeldt-Jakob Disease, Eur. J. Hum. Genet., 2004, vol. 12, pp. 389–394.PubMedCrossRefGoogle Scholar
  9. 9.
    Brandel, J.P., Preece, M., Brown, P., et al., Distribution of Codon 129 Genotype in Human Growth Hormone-Treated CJD Patients in France and the UK, Lancet, 2003, vol. 362, pp. 128–130.PubMedCrossRefGoogle Scholar
  10. 10.
    Deslys, J., Marce, D., and Dormont, D., Similar Genetic Susceptibility in Iatrogenic and Creutzfeldt-Jakob Disease, J. Gen. Virol., 1994, vol. 75, pp. 23–27.PubMedCrossRefGoogle Scholar
  11. 11.
    Soldevila, M., Calafell, F., Andres, A., et al., Prion Susceptibility and Protective Alleles Exhibit Marked Geographic Differences, Hum. Mutat., 2003, vol. 22, no. 1, pp. 104–105.PubMedCrossRefGoogle Scholar
  12. 12.
    Soldevila, M., Andres, A., Ramirez-Soriano, A., et al., The Prion Protein Gene in Humans Revisited: Lessons from a Worldwide Resequencing Study, Genome Res., 2006, vol. 16, pp. 231–236.PubMedCrossRefGoogle Scholar
  13. 13.
    Zavalishin, I.A., Zakharova, M.N., Zhuchenko, T.D., and Peresedova, A.V., Ethiology and Pathogenesis of Multiple Sclerosis, in Rasseyannyi skleroz: Izbrannye voprosy teorii i praktiki (Multiple Sclerosis: Selected Issues of Theory and Practice), Moscow: NII nevrologii RAMN, 2000, pp. 537–579.Google Scholar
  14. 14.
    Woitowicz, S., Multiple Sclerosis and Prions, Med. Hypotheses, 1993, vol. 40, no. 1, pp. 48–54.CrossRefGoogle Scholar
  15. 15.
    Wells, T., Multiple Sclerosis Genes Step out of the Shadows, Business Briefing: Future Drug Discovery, Boulton, E., Ed., London: World Markets Research Center, 2006, pp. 50–52. ( Scholar
  16. 16.
    McDonald, W.I., Compston, A., Edan, G., et al., Recommended Diagnostic Criteria for Multiple Sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis, Ann. Neurol., 2001, vol. 50, no. 1, pp. 121–127.PubMedCrossRefGoogle Scholar
  17. 17.
    Newton, C.R., Graham, A., Heptinstall, L.E., et al., Analysis of any Point Mutation DNA: The Amplification Refractory Mutation System (ARMS), Nucleic Acids Res., 1989, vol. 17, no. 7, pp. 2503–2516.PubMedCrossRefGoogle Scholar
  18. 18.
    Zhivotovsky, L.A., Populyatsionnaya biometriya (Population Biometry), Moscow: Nauka, 1991.Google Scholar
  19. 19.
    Bland, J.M. and Altman, D.G., The Odds Ratio, BMJ, 2000, vol. 320, p. 1468.PubMedCrossRefGoogle Scholar
  20. 20.
    Mitrova, E., Mayer, V., Jovankovicova, V., et al., Creutzfeldt-Jakob Disease Risk and PRNP Codon 129 Polymorphism: Necessity to Revalue Current Data, Eur. J. Neurol., 2004, vol. 12, pp. 998–1001.CrossRefGoogle Scholar
  21. 21.
    Bratosiewicz, J., Liberski, P., Kulczycki, J., et al., Codon 129 Polymorphism of the PRNP Gene in Normal Polish Population and in Creutzfeldt-Jakob Disease and the Search for New Mutations in PRNP Gene, Acta Neurobiol. Exp., 2001, vol. 61, pp. 151–156.Google Scholar
  22. 22.
    Rujescu, D., Hartmann, A., Gonnermann, C., et al., M129V Variation in the Prion Protein May Influence Cognitive Performance, Mol. Psychiatry, 2003, vol. 8, pp. 937–941.PubMedCrossRefGoogle Scholar
  23. 23.
    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, vol. 55, pp. 593–595.PubMedGoogle Scholar
  24. 24.
    Zimmermann, K., Turecek, P., and Schwarz, H., Genotyping of the Prion Protein Gene at Codon 129, Acta. Neuropathol., 1999, vol. 97, pp. 355–358.PubMedCrossRefGoogle Scholar
  25. 25.
    Plaitakis, A., Viskadouraki, A., Tzagournissakis, M., et al., Increased Incidence of Sporadic Creutzfeldt-Jakob Disease on the Island of Grete Associated with a High Rate of PRNP 129-Metionine Homozygosity in the Local Population, Ann. Neurol., 2001, vol. 50, pp. 227–233.PubMedCrossRefGoogle Scholar
  26. 26.
    Nurmi, M., Bishop, M., Strain, L., et al., The Normal Population Distribution of PRNP Codon 129 Polymorphism, Acta Neurol. Scand., 2003, vol. 108, pp. 374–378.PubMedCrossRefGoogle Scholar
  27. 27.
    Salvatore, M., Genuardi, M., Petraroli, R., et al., Polymorphism of the Prion Protein Gene in Italian Patients with Creutzfeldt-Jakob Disease, Hum. Genet., 1994, vol. 94, pp. 375–379.PubMedCrossRefGoogle Scholar
  28. 28.
    Laplanche, J., Delasnerie-Laupretre, N., Brandel, J., et al., Molecular Genetics of Prion Diseases in France: French Research Group on Epidemiology of Human Spongiform Encephalopathies, Neurology, 1994, vol. 44, pp. 2347–2351.PubMedGoogle Scholar
  29. 29.
    Collinge, J., Palmer, M., and Dryden, A., Genetic Predisposition to Iatrogenic Creutzfeldt-Jakob Disease, Lancet, 1991, vol. 337, pp. 1441–1442.PubMedCrossRefGoogle Scholar
  30. 30.
    Georgsson, G., Tryggvason, T., Jonasdottir, A., et al., Polymorphism of PRPN Codons in the Normal Icelandic Population, Acta Neurol. Scand., 2006, vol. 113, pp. 419–425.PubMedCrossRefGoogle Scholar
  31. 31.
    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., 2001, vol. 9, pp. 965–968.PubMedCrossRefGoogle Scholar
  32. 32.
    Brown, P., Cervenakova, L., Goldfarb, L., et al., Iatrogenic Creutzfeldt-Jakob Disease: An Example of the Interplay between Ancient Genes and Modern Medicine, Neurology, 1994, vol. 44, pp. 291–293.PubMedGoogle Scholar
  33. 33.
    Jeong, B., Nam, J., Lee, K., et al., Polymorphisms of the Prion Gene (PRNP) in a Korean Population, J. Hum. Genet., 2004, vol. 49, pp. 319–324.PubMedCrossRefGoogle Scholar
  34. 34.
    Doh-Ura, K., Kitamoto, T., Sakaki, Y., and Tateishi, J., CJD Discrepancy, Nature, 1991, vol. 358, pp. 801–802.CrossRefGoogle Scholar
  35. 35.
    Tsai, M.T., Su, Y.C., Chen, Y.H., and Chen, C.H., Lack of Evidence to Support the Association of the Human Prion Gene with Schizophrenia, Mol. Psychiatry, 2001, vol. 6, pp. 74–78.PubMedCrossRefGoogle Scholar
  36. 36.
    Parchi, P., Capellari, S., and Chin, S., A Subtype of Sporadic Prion Disease Mimicking Fatal Familial Insomnia, Neurology, 1999, vol. 52, no. 9, pp. 1757–1763.PubMedGoogle Scholar
  37. 37.
    Dermaut, B., Croes, E., and Rademakers, R., PRNP Val129 Homozygosity Increases Risk for Early-Onset Alzheimer’s Disease, Ann. Neurol., 2003, vol. 53, pp. 409–412.PubMedCrossRefGoogle Scholar
  38. 38.
    Riemenschneider, M., Klopp, N., Xiang, W., et al., Prion Protein Codon 129 Polymorphism and Risk of Alzheimer Disease, Neurology, 2004, vol. 63, pp. 364–366.PubMedGoogle Scholar
  39. 39.
    Del Bo, R., Scarlato, M., Ghezzi, S., et al., Is M129V of PRNP Gene Associated with Alzheimer’s Disease? A Case-Control Study and a Meta-Analysis, Neurobiol. Aging., 2006, vol. 27, no. 5, p. 770.e1–770.e5.CrossRefGoogle Scholar
  40. 40.
    Berr, C., Richard, F., Dufouil, C., et al., Polymorphism of the Prion Protein is Associated with Cognitive Impairment in the Elderly: The EVA Study, Neurology, 1998, vol. 51, pp. 734–737.PubMedGoogle Scholar
  41. 41.
    Croes, E.A., Dermaut, B., and Houwing-Duistermaat, J., Early Cognitive Decline is Associated with Prion Protein Codon 129 Polymorphism, Ann. Neurol., 2003, vol. 54, pp. 275–276.PubMedCrossRefGoogle Scholar
  42. 42.
    Li, X., Rowland, L., Mitsumoto, H., et al., Prion Protein Codon 129 Genotype Prevalence is Altered in Primary Progressive Aphasia, Ann. Neurol., 2005, vol. 58, pp. 858–864.PubMedCrossRefGoogle Scholar
  43. 43.
    Grubenbencher, S., Stuve, O., Hefter, H., and Korth, C., Prion Protein Gene Codon 129 Modulates Clinical Course of Neurological Wilson Disease, Neuroreport, 2006, vol. 17, pp. 549–552.CrossRefGoogle Scholar
  44. 44.
    Scholz, S., Xiromerisiou, G., Fung, H., et al., The Human Prion Gene M129V Polymorphism Is not Associated with Idiopathic Parkinson’s Disease in Three Distinct Populations, Neurosci. Lett., 2006, vol. 395, pp. 227–229.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2009

Authors and Affiliations

  • O. V. Chubukova
    • 1
  • O. E. Mustafina
    • 1
  • A. V. Chemeris
    • 1
  • I. A. Tuktarova
    • 1
  • K. Z. Bahtijarova
    • 1
  • R. V. Magjanov
    • 2
  • Yu. M. Nikonorov
    • 1
  1. 1.Institute of Biochemistry and Genetics, Ufa Research CenterRussian Academy of SciencesUfaRussia
  2. 2.Bashkir State Medical UniversityUfaRussia

Personalised recommendations