NR AXWN
AU Slivarichova,D.; Mitrova,E.; Koscova,S.; Uhnakova,I.
TI Slovak Accumulation of Genetic Creutzfeldt-Jakob Disease with Exogenous Risk Factor
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.57
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
CJD specific mutation at the PRNP gene - E200K in slovak carriers is characterized by incomplete penetrance (59%). Therefore for clinical manifestation of the disease also other endo- or exogenous factors could not be excluded. Several experimental studies demonstrated that levels of Cu, Mn are probably essential for PrPc stability. Previously we demonstrated Mn/Cu disbalance in the soil and food chain in the slovak area of focal genetic CJD accumulation as a result of environmental Mn contamination by factories with ferroalloys production. The aim of study was to clarify the possible role of these metals in the development of clinical manifestation of the disease and their exogenous influence on the focal CJD accumulation in Slovakia. Mn, Cu levels in brain tissue were determined by flame atomic absorption spectrometry (18 genetic cases were devided into 2 subgroups in regard to their origin - 9 cases from CJD region, 9 out of CJD region, 18 sporadic cases, 18 negative controls).
Analyses demonstrate i) increased Mn levels in genetic "CJD region" and sporadic CJD in comparison to controls. Mn level in genetic "CJD region" cases is significantly higher in comparison to all other groups; ii) Cu status differences between groups are not statistically significant, decreased concentration has been found in genetic cases "out of CJD region"; iii) Mn/Cu ratios are increased in all CJD groups in comparison to controls. Metal ratios in genetic "CJD region" cases are significantly higher in comparison to sporadic cases and also to controls, but not to the other genetic subgroup.
Results support data demonstrating the involvement of investigated metals in the pathogenesis of CJD. More important than Mn/Cu absolute levels is the metal disbalance since it was detected in the CNS of both genetic subgroups as well as in sporadic cases. The reasons of Mn/Cu disturbance ratios are different: in genetic "CJD region" cases it is linked with the excessive environmental Mn level in the area, in genetic cases from the rest of Slovakia this disbalance is caused by decreased Cu level (at present of unknown reason). Our data indicate the environmental Mn/Cu disbalance as a possible exogenous CJD-risk factor which may in coincidence with verified endogenous (genetic) risk contribute to the focal accumulation of genetic CJD in Slovakia. Work was supported by Science and Technology Assistance Agency, contract No. APVT-21-019004.
AD D. Slivarichova, E. Mitrova, S. Koscova, Slovak Medical University, Department of Prion Diseases, Slovakia; I. Uhnakova, Slovak Medical University, Laboratory of Toxic and Essential Elements, Slovakia
SP englisch
PO Schottland