The Role of Acetyl-L-Carnitine Levels and 95A > G Mutations in the SLC22A5 Gene on Parkinson's Disease in Faroe Islands

Objective: The role of mitochondrial functions, as well as increased oxidative stress, has been proposed in the pathogenesis of Parkinson’s disease (PD). Putative neuroprotective agents, e.g. carnitine, have been proposed to have beneficial effects in preventing the loss of brain functions which typically occur during aging and neurodegenerative disorders. Background: The aim of this study was to investigate the contribution of low carnitine levels to the risk of developing PD in the Faroese population where the prevalence of both PD and carnitine transporter deficiency (CTD) is high. CTD is an autosomal recessive disorder caused by a 95A>G mutations in the SLC22A5 gene encoding for the high affinity carnitine transporter OCTN2 leding to low tissue carnitine levels and an impaired fatty acid oxidation. Method: We conducted a case-control study where 121 PD patients were studies for free carnitine and total carnitine levels and genetic mutation in the SLC22A5 gene against 235 randomly selected controls, matched by gender and age. Carnitine was determined by tandem mass spectrometry (MS/MS) and sequencing was performed with ABI PRISM 7000 Sequence Detection System. Results: Significant difference was observed in free and total carnitine levels between PD cases and controls (P<0.001) but no difference was found in mutation frequency in the SLC22A5 gene (P=0.70); however mutation carrier had significantly lower levels compared with non-carriers (P<0.001). Conclusion: Faroese PD patients have significantly lower carnitine levels compared to controls which cannot be explained by higher frequency of mutation in the SLC22A5 gene. However, this finding has to be explored further.