Mitochondrial DNA Partly Point Mutations In Manganese-induced Parkinsonism

Objective: To test the association between mitochondrial DNA (mtDNA)point mutations and manganese-induced Parkinsonism. To study the relation ofmtDNA polymorphisms with susceptibility to occupational chronic manganism.Methods: Twenty-eight patients with manganese-induced Parkinsonism andthirty-seven controls who aren’t manganese-induced Parkinsonism patients insame environment with patients and thirty healthy controls were enrolled in thisstudy. Polymerase Chain Reaction (PCR) was used to amplifymtDNA1709,3196,4336,5460,9055,10398,13513,13708and ND1gene region.For the PCR products were screened for mutations using a combination of single‐stranded conformation polymorphism (SSCP) analysis and the abnormalsegments were sequenced. SNP frequencies were compared by the χ2test.Results: Three mtDNA point mutation G3885A, four mtDNA pointmutation C4253G, seven mtDNA point mutation G9053A, three mtDNA pointmutation C9193A and two mtDNA point mutation A10398G, C10400T wasdetected in manganese-induced parkinsonism patients. One mtDNA pointmutation C9193A, three mtDNA point mutation A10219C and fifteen mtDNApoint mutation A10398G, C10400T was detected in manganese exposure group. One mtDNA point mutation G9053A and one mtDNA point mutation C9193Awas detected in healthy group. The frequencies of three SNPs (C4253G,G9053A,A10398G, C10400T) were found to be significantly different (P≤0.05) between the patient group and two control groups. However,we have notfound any mutations among mtDNA1709,3196,4336,5460,9055,13513,13708．The frequency of the mumber ofaccumulated mutations in Manganese Working Group(manganese-inducedParkinsonism patients and manganese exposure group) was higher comparedwith non-Mn Group.Conclusions:The results suggest that the SNP (C4253G) and SNP (G9053A)increase risk of developing manganese-induced Parkinsonism, whereasA10398G and C10400T had protective effects or were a linked protectionmutation. Our study showed that mtDNA C4253G was possiblly a newpathogenic polymorphism. We did not find a significant association betweenmanganese-induced Parkinsonism and thesepolymorphisms(np1709,G3196A,A4336G,G5460A,G9055A,np13513,G13708A). Manganese accumulation could increase the risk of DNAmutations.