Slivarichová Dana, Mitrová Eva, Ursínyová Monika, Uhnáková Iveta, Koscová Silvia, Wsólová Ladislava
Department of Prion Diseases, Slovak Medical University, Bratislava, Slovak Republic.
Cent Eur J Public Health. 2011 Sep;19(3):158-64. doi: 10.21101/cejph.a3667.
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 significance; 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.
斯洛伐克的特点是，受朊蛋白基因E200K突变所致的遗传性克雅氏病（CJD）影响的患者数量异常之多。该突变的外显率并不完全（59%）。因此，对于临床表现的出现，不能排除其他内源性或外源性因素的影响。实验数据表明，铜和锰水平可能在朊病毒疾病的发病机制中发挥重要作用。斯洛伐克遗传性CJD患者数量最多的地区是奥拉瓦——斯洛伐克中部的北部地区。锰是奥拉瓦地区的主要污染物。本研究的目的是阐明环境中锰/铜失衡对CJD聚集现象可能产生的外源性影响。对遗传性CJD病例（来自奥拉瓦和斯洛伐克的对照地区）以及散发性CJD患者和对照者的脑组织中的锰和铜水平进行了分析。分析表明：i）与所有其他组相比，局部聚集的“集群性”遗传性CJD病例中的锰水平显著更高；ii）各比较组之间的铜状态差异无统计学意义；在非局部遗传性CJD地区的遗传病例中发现铜浓度降低；iii）与对照组相比，所有CJD组中的锰/铜比值均升高。与散发性病例和对照组相比，集群性gCJD病例中的金属比值显著更高，但与非局部遗传性CJD亚组相比则不然。这些结果表明，在CJD发病机制中，锰/铜失衡在中枢神经系统中的作用似乎比锰水平升高更为重要。在遗传性CJD病例集群中观察到的失衡可能是以下两者共同作用的结果：环境中锰水平过高以及奥拉瓦地区锰/铜比值的紊乱。研究结果表明，环境中锰/铜失衡可能是CJD的一种外源性风险辅助因素，它可能与内源性（遗传）CJD风险共同作用，导致斯洛伐克遗传性CJD的局部聚集（集群）。
