Investigation of the Association of Homocysteine and MTHFR Polymorphisms and Treatment Options in Parkinson’s disease in Turkey

Öz

Aim In this study, we aimed to investigate the effects of MTHFR C677T and A1298C polymorphisms to homocysteine levels in patients with Parkinson's disease who were treated with levodopa and entekapone. Material and Methods Plasma homocysteine (hcy), folat and vitamin B12 and MTHFR (C677T, A1298C) polymorphisms and treatment options were compared in 70 Parkinson's Disease (PD) patients whom taking levodopa (n=26), dopamine agonist (n=11) and levodopa and entacapone treatment together (n=33) with 100 controls. Results Although no statistically significant difference was detected, hcy level of the patients was found higher compared to control group (patient 18.29 ± 9.22 µmol /l vs control 15.77 ± 7.58 µmol / l; p> 0,05) and hcy level was highest in the patients receiving only levodopa, too (19.56 ± 10.77 µmol / l; p> 0,05). The frequency of TT genotype in the patients was higher compared to the control group (11.4%, 6%, P < 0.05). Especially, hcy level for levodopa-receiving patients with 677TT genotype was become significantly higher level when compared with other genotypes of levodopa-receiving patients (respectively 677TT 36.28 ± 16.17, 677CT 13.5 ± 1.71, 677CC 17.2 ± 6.59 P < 0.01). No statistically significant difference was detected between patients and controls regarding their folat and vitamin B12 levels and A1298C polymorphism (p> 0, 05). Conclusions Finally, we concluded that both 677TT genotype and levodopa treatment might be jointly contributed to the increasing of the plasma hcy levels in PD patients and entacapone limitedly decreased hcy levels during levodopa treatment but results need to be confirmed with larger sample sized comprehensive studies.

Anahtar Kelimeler

• Anahtar levodopa, hiperhomosisteinemi

References

1. Finkelstain J D. Homocysteine: A history in progress. Nutr Rev 2000;58(7):193-204. 2. Shelhub J, Miller JW. The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and.transsulfuration of homocysteine. Am J Clin Nutr 1992;55(1):131-8.
2. Ogier de Baulny H, Gerard M, Saudubray JM, Zittoun J. Remethylation defects:guidelines for clinical diagnosis and treatment. Eur J Pediatr 1998;157 :(suppl 2) S 77-83.
3. Rosenblatt DS. Inherited disorders of folic acid transport and metabolism. 1995 In: Scriver CR, 1995
4. Beaudet AL, Sly S, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 1995 Seventh ed. 3111–3128. New-York: McGraw-Hill.
5. Woitalla D, Kuhn W, Muller T. MTHFR 677T polymorphism, folic acid and hyperhomocysteinemia in levodopa treated patients with Parkinson’s disease. J Neural Trans Suppl. 2004;68:15-20.
6. Weisberg IS, Jacques PF, Selhub J, Bostom AG, Chen Z, Curtis Ellison R, et al. The 1298A−>C polymorphism in methylenetetrahydrofolic acid reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis 2001;156(2):409–15.
7. Kuhn, W, Roebroek R, Blom H, van Oppenraaij D, Przuntek H, Kretschmer A, et al. Elevate plasma levels of homocysteine in Parkinson’s disease. Eur Neurol 1998;40(4):225-7.
8. Blandini F, Facellu R, Martignoni E, Mangiagalli A, Pacchetti C, Samuele A, et al. Plasma homocysteine and L-dopa metabolism in patients with Parkinson’s disease. Clin Chem 2001;47(6):1102-4.

9. Yuan RY, Sheu JJ, Yu JM, Hu CJ, Tseng IJ, Ho CS, et al. Methylenetetrahydrofolic acid reductase polymorphisms and plasma homocysteine in levodopa-treated and non- treated Parkinson's disease patients. J Neurol Sci. 2009; 15;287(1-2):64-8.
10. Miller JW, Selhub J, Nadeau MR, Thomas CA, Feldman RG, Wolf PA. Effect of L-dopa on plasma homocysteine in PD patients: relationship to B-vitamin status. Neurology 2003;60(7):1125–9.
11. Miller JW, Shukitt-Hale B, Villalobos-Molina R, Nadeau MR, Selhub J, Joseph JA. Effect of L-Dopa and the Catechol-O-Methyltrensferase inhibitor Ro 41-0960 on sulphur amino acid metabolites in rats. Clin Neuropharmacol 1997;20(1):55–66.
12. Yassin MS, Cheng H, Ekblom J, Oreland L. Inhibitors of catecholamine metabolizing enzymes cause changes in S-adenosylmethionine and S-adenosylhomocysteine in the rat brain. Neurochem Int 1998;32(1):53–9.
13. Muller T, Werne B, Fowler B, Kuhn W. Nigral endothelial dysfunction, homocysteine, and Parkinson's disease. Lancet 1999;10;354(9173):126-7
14. Caccamo D, Gorgone G, Curro M, Parisi G, Di Ioiro W, Menichetti C, et al. Effect of MTHFR Polymorphisms on Hyperhomocysteinemia in
15. Levodopa-treated Parkinsonian Patients.
16. Neuromolecular Med 2007;9(3):249-254.
17. Todorovic Z, Dzoljic E, Novakovic I, Mirkovic D, Stojanovic R, Nesic Z, et al. Homocysteine serum levels and MTHFR C677T genotype in patients with Parkinson's disease, with and without levodopa therapy. J Neurol Sci 2006;25;248(1-2):56-61.
18. Zhao P, Yang JF, Liu W, Wang Y, Sun YN, Li Q, Zhang W, Zhang BS. Effects of entacapone on plasma homocysteine in Parkinson's disease patients on levodopa. Zhonghua Yi Xue Za Zhi. 2013;19;93(7):512-5.