Coenzyme Q10, hyperhomocysteinemia and MTHFR C677T polymorphism in levodopa-treated Parkinson's disease patients

Gaetano Gorgone, Monica Currò, Nadia Ferlazzo, Giulia Parisi, Lucilla Parnetti, Vincenzo Belcastro, Nicola Tambasco, Aroldo Rossi, Francesco Pisani, Paolo Calabresi, Riccardo Ientile, Daniela Caccamo

Research output: Contribution to journalArticlepeer-review

Abstract

There is evidence that increased homocysteine (Hcy) levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects. Homocysteine neurotoxicity mainly relies on redox state alterations. The present work was aimed at investigating the relationships between plasma Hcy concentrations and percent content of oxidized versus total Coenzyme Q10 (%CoQ10) in 60 PD patients and 82 healthy subjects. Both groups were screened for plasma levels of Hcy, vitamin B12, folate, %CoQ10 and C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism. The MTHFR TT677 mutated genotype was found more frequently in patients than in controls (p = 0.01). In a multivariate analysis, Hcy levels and %CoQ10 were associated with the case/control category (p <0.0001), MTHFR genotype (p <0.0001) and their interaction term (p = 0.0015), even after adjusting for age, sex, folate and vitamin B12. Patients carrying the TT677 genotype exhibited the highest values of Hcy and %CoQ10 (p <0.0001). Structural equation modelling evidenced that the TT677 genotype and levodopa daily dose were independently and directly correlated with Hcy (p <0.0001, and p = 0.003, respectively), which, in turn, showed a significant correlation (p <0.0001) with the %CoQ10 in PD patients. Our results suggest that increased Hcy levels act as mediator of the systemic oxidative stress occurring in PD, and %CoQ10 determination might be regarded as a predictor of toxic Hcy effects.

Original languageEnglish
Pages (from-to)84-90
Number of pages7
JournalNeuroMolecular Medicine
Volume14
Issue number1
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Coenzyme Q10
  • Homocysteine
  • Levodopa
  • MTHFR polymorphisms
  • Parkinson's disease

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Neurology

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