Effect of MTHFR polymorphisms on hyperhomocysteinemia in levodopa-treated Parkinsonian patients

D. Caccamo, G. Gorgone, M. Currò, G. Parisi, W. Di Iorio, C. Menichetti, V. Belcastro, L. Parnetti, A. Rossi, F. Pisani, R. Ientile, P. Calabresi

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Abstract

High plasma homocysteine levels have been observed in Parkinson's disease (PD) patients treated with levodopa. In this study, we investigated the effects of C677T and A1298C MTHFR polymorphisms, in association with l-DOPA daily dose and vitamin status, on hyperhomocysteinemia development in PD patients. Plasma homocysteine and folate/vitamin B12 levels were assayed in 49 l-DOPA-treated PD patients, and compared with those of 86 healthy subjects. Genotyping for MTHFR polymorphisms was carried out by DG-DGGE. Homocysteine levels were significantly higher in patients than in controls (16.3 ± 5.7 vs. 11.7 ± 2.7 μmol/l, P <0.01). No significant differences were found between patients and controls with regard to folate/vitamin B12 levels, and MTHFR allele distribution. The TT+AA genotype was significantly more frequent in PD patients than in controls (32.5% vs. 17.4%, P <0.05), but not associated with an increased risk for PD (OR ≤ 2.3, CI ≤ 1.0-5.2). Further, patients carrier of this genotype exhibited a mild hyperhomocysteinemia (22.1 ± 4.9 μmol/l), while a protective effect was observed in patients having the CC+AA genotype (11.2 ± 1.6 μmol/l; OR ≤ 0.19, CI ≤ 0.06-0.59). Interestingly, homocysteine levels were also moderately increased in patients with CT heterozygous genotype, in the context of either AA or AC (14.5 ± 3.6 μmol/l), in comparison to subjects with the CC + AA genotype. Finally, we did not find any significant association of combined C677T and A1298C MTHFR polymorphisms with an increased risk for hyperhomocysteinemia in PD patients. A better understanding of the role of homocysteine and MTHFR genotypes in PD is needed to reveal novel approaches for disease management.

Original languageEnglish
Pages (from-to)249-254
Number of pages6
JournalNeuroMolecular Medicine
Volume9
Issue number3
DOIs
Publication statusPublished - Sep 2007

Keywords

  • Folate
  • Homocysteine
  • Levodopa
  • MTHFR genotypes
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Cell Biology

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  • Cite this

    Caccamo, D., Gorgone, G., Currò, M., Parisi, G., Di Iorio, W., Menichetti, C., Belcastro, V., Parnetti, L., Rossi, A., Pisani, F., Ientile, R., & Calabresi, P. (2007). Effect of MTHFR polymorphisms on hyperhomocysteinemia in levodopa-treated Parkinsonian patients. NeuroMolecular Medicine, 9(3), 249-254. https://doi.org/10.1007/s12017-007-8006-x