Manganese-Induced Parkinsonism And Mitochondrial Cytochromeb Partly Mutations

Manganese(Mn),is an important and essential nutrient for proper health and maintenance.It is toxic in high doses ,and exposure to excessive levels can result in the onset of a neurological disorder similar to,but distinct from,Parkinson's disease.Occupational manganese poisoning is one of the most common occupational diseases in china .In humans , Manganese selectively accumulate in cells rich in mitochondria. Chronic manganism causes an extrapyramidal syndrome with features resembling those found in Parkinson's disease and postencephalitic parkinsonism.Patients with motor disturbances caused by manganese can live for many years after exposure has ceased.Mitochondria has key role in energy metabolism of all cells and tissues. Mitochondrial DNA single nucleotide polymorphisms(SNPs) change the Function of the electron transport chain(ETC),which lead to energy metabolism changes .Cytochrome b(CYTB) on mitochondrial DNA is reported to be closely linked with myopathy and neurological disability ,which indicates the effect of CYTB SNP on muscle and nerve energy metabolism.Occupational epidemiological studies have shown that manganese exposure is the major risk factor for manganism.the fact that only a fraction of workers exposed to manganese develop nervous system dysfunction suggests the presence of a genetic predisposition in some individuals.The susceptibility factors for manganism may include genetically determined variations in metabolic enzymes such as the Mitochondrial DNA CYTB gene. Through this study,we want to find the relationship between manganese-induced parkinsonism and mitochondrial cytochromeb partly mutations.Objective:To investigate the relationship between manganese—induced parkinsonism and mitochondrial cytochromeB partly mutations.Methods:Twenty patients with manganese—induced parkinsonism and forty patients who have also the same age and work environment as the manganism patients but did not diagnose as manganese-induced parkinsonism,and forty healthy controls were enrolled in this study.Polymerase chain reaction (PCR)was used to amplify three mtDNA segments of all participants,including all the CYTB gene region.For the PCR products of mtDNA CYTB gene region,single strand conformation polymorphism(SSCP)was adopted to detect mutations and the abnormal segments were sequenced.SPSS 16.0 statistics software was used to analysis the results. Results:1,Five mtDNA point 15024 G>A mutation was detected in fourmanganese-induced parkinsonism patients .The incidence of this point mutation in parkonsonism patients is higher than the manganese exposure group and the the healthy control group.2,Five mtDNA point 15301 G>A and 15326 A>G synchronous mutation was detected in manganese exposure group,while the other two group do not.3,The number of people with Point mutation and the number of accumulated mutations in Manganese Working Group both more than non-Mn Group.?In addition, the proportion and the frequency of the mumber of people with≥3 point mutation yileded higher compared with non-Mn Group.Conclusion: 1,The mtDNA point 15043 G>A mutation may be associated withsusceptibility to chronic manganism or may be involved in the pathogenesis of manganese-induced parkinsonism,but this should be confirmed by future large sample and well designed study.2,Manganese accumulation could attack the CYTB gene region of mitochondrial DNA, and increased the risk of DNA mutations.