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GEOGRAPHIC ACCUMULATION OF CREUTZFELDT- JAKOB DISEASE IN SLOVAKIA ? ENVIRONMENTAL METAL IMBALANCE AS A POSSIBLE COFACTOR

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  • GEOGRAPHIC ACCUMULATION OF CREUTZFELDT- JAKOB DISEASE IN SLOVAKIA ? ENVIRONMENTAL METAL IMBALANCE AS A POSSIBLE COFACTOR

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    https://www.researchgate.net/publica...sible_Cofactor
    Cent Eur J Public Health 2011; 19 (3): 158?164
    SUMMARY
    Slovakia is characterised by an unusually high number of patients affected by genetic Creutzfeldt-Jakob disease (CJD) with E200K mutation
    at the PRNP gene. Penetrance of the mutation is incomplete (59%). Therefore, for the onset of the clinical manifestation, an influence of other
    endo- or exogenous factors could not be excluded. Experimental data suggest that copper and manganese levels may play an important role in
    the pathogenesis of prion diseases. The highest number of Slovak genetic CJD patients originates from Orava ? the northern region of central
    Slovakia. Manganese is a dominant pollutant in Orava. The objective of this study was to clarify a possible exogenous influence of environmental
    Mn/Cu imbalance on the CJD clustering. Mn and Cu levels were analysed in the brain tissue of genetic CJD cases (from Orava and from control
    regions of Slovakia), as well as of sporadic CJD patients and controls. Analyses demonstrate i) significantly higher Mn level in focally accumulated,
    ?clustering? genetic CJD cases in comparison to all other groups, ii) Cu status differences between compared groups were without statistical sig-
    nificance; decreased concentrations were found in genetic cases from extrafocal genetic CJD areas, iii) Mn/Cu ratios were increased in all CJD
    groups in comparison to controls. Metal ratios in clustering gCJD cases were significantly higher in comparison to sporadic cases and also to
    controls, but not to the extrafocal genetic CJD subgroup. These results indicate that more important than increasing Mn level in pathogenesis of
    CJD appears to be the role of the Mn/Cu imbalance in the CNS. The imbalance observed in the cluster of genetic CJD cases is probably a result of
    both: the excessive environmental Mn level and the disturbance of Mn/Cu ratios in the Orava region. Presented findings indicate an environmental
    Mn/Cu imbalance as a possible exogenous CJD risk co-factor which may, in coincidence with endogenous (genetic) CJD risk, contribute to the
    focal accumulation (cluster) of genetic CJD in Slovakia.
    Key words: manganese, copper, metal imbalance, Creutzfeldt-Jakob disease, cluster
    Address for correspondence: D. Slivarichov?, Department of Prion Diseases, Slovak Medical University, Limbov? 12, 833 03 Bratislava, Slovak
    Republic.
    GEOGRAPHIC ACCUMULATION OF CREUTZFELDT-
    JAKOB DISEASE IN SLOVAKIA ? ENVIRONMENTAL
    METAL IMBALANCE AS A POSSIBLE COFACTOR
    Dana Slivarichov?1, Eva Mitrov?1, Monika Urs?nyov?2, Iveta Uhn?kov?2, Silvia Ko?čov?1, Ladislava Ws?lov?3
    1Department of Prion Diseases, Slovak Medical University, Bratislava, Slovak Republic
    2Laboratory of Toxic and Essential Elements, Slovak Medical University, Bratislava, Slovak Republic
    3Department of Biostatistical Analysis, Slovak Medical University, Bratislava, Slovak Republic
    _____________________________________________

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