Cent Eur J Public Health 2011, 19(3):158-164 | DOI: 10.21101/cejph.a3667

Geographic Accumulation of Creutzfeldt-Jakob Disease in Slovakia - Environmental Metal Imbalance as a Possible Cofactor

Dana Slivarichová¹, Eva Mitrová¹, Monika Ursínyová², Iveta Uhnáková², Silvia Koščová¹, Ladislava Wsólová³

¹ Department of Prion Diseases, Slovak Medical University, Bratislava, Slovak Republic

² Laboratory of Toxic and Essential Elements, Slovak Medical University, Bratislava, Slovak Republic

³ Department of Biostatistical Analysis, Slovak Medical University, Bratislava, Slovak Republic

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.

Keywords: manganese, copper, metal imbalance, Creutzfeldt-Jakob disease, cluster

Received: January 31, 2011; Revised: May 19, 2011; Accepted: May 19, 2011; Published: September 1, 2011  Show citation