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Vol. 48, No. 4, 2003
Issue release date: December 2003

Association between Catechol-O-Methyltransferase Gene Polymorphisms and Wearing-Off and Dyskinesia in Parkinson’s Disease

Watanabe M. · Harada S. · Nakamura T. · Ohkoshi N. · Yoshizawa K. · Hayashi A. · Shoji S.
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Abstract

Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines, including levodopa. An amino acid change (Val-108-Met) in the COMT protein has been found to result in a change from high to low enzyme activity. In the present study, we genotyped 121 Japanese patients with Parkinson’s disease (PD) and 100 controls. Comparison of the allele frequencies revealed that homozygosity for the low-activity allele was significantly more common among PD patients than the controls (p = 0.047, odds ratio = 3.23). In addition, homozygosity for the low-activity allele was overrepresented in PD patients that exhibited the ‘wearing-off’ phenomenon (p = 0.045, odds ratio = 3.82) or dyskinesia (p = 0.030, odds ratio = 4.80) compared with controls, although these differences were not significant after Bonferroni’s correction. Our results may help understand the mechanism that cause complications of levodopa therapy in PD patients.



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References

  1. Marsden CD: Parkinson’s disease. Lancet 1990;335:948–952.
  2. Sweet RD, McDowell FH: Five years’ treatment of Parkinson’s disease with levodopa: Therapeutic results and survival of 100 patients. Ann Intern Med 1975;83:456–463.
  3. Hely MA, Morris JGL, Reid WGJ, O’Sullivan DJ, Williamson PM, Rail D, Broe GA, Margrie S: The Sydney Multicentre Study of Parkinson’s disease: A randomized, prospective five-year study comparing low dose bromocriptine with low dose levodopa-carbidopa. J Neurol Neurosurg Psychiatry 1994;57:903–910.
  4. Block GA, Liss CL, Reines S, Irr J, Nibblelink D, CR First Study Group: Comparison of immediate-release and controlled release carbidopa/levodopa in Parkinson’s disease. Eur Neurol 1997;37:23–27.
  5. Jellinger K, Kienzl E, Rumpelmaier G, Riederer P, Paulus W, Stachelberger H, Youdim MBH, Ben-Shachar D: Iron-melanin complex in substantia nigra of parkinsonian brains: An X-ray microanalysis. J Neurochem 1993;59:1168–1171.
  6. Nutt JG, Woodward WR, Beckner RM: Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology 1994;44:913–919.
  7. Routtinen HM, Rinne UK: Entacapone prolongs levodopa response in a one-month double-blind study in parkinsonian patients with levodopa-related fluctuations. J Neurol Neurosurg Psychiatry 1996;60:36–40.
  8. Axelrod J, Tomchick R: Enzymatic O-methylation of epinephrine and other catechols. J Biol Chem 1958;233:702–705.
  9. Weishilboum RM, Raymond FA: Inheritance of low erythrocyte catechol-O-methyltransferase activity in man. Am J Hum Genet 1977:29:125–135.
  10. Boudikova B, Szumlanski C, Maidak B, Weinshilboum RM: Human liver catecholamine-O-methyltransferase pharmacogenetics. Clin Pharmacol Ther 1990;48:381–389.
  11. Askoy S, Klener J, Weinshilboum RM: Catechol-O-methyltransferase pharmacogenetics: Photoaffinity labelling and Western blot analysis of human liver samples. Pharmacogenetics 1993;3:116–122.
  12. Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melen K, Julkunen I, Taskinen J: Kinetics of human soluble and membrane-bound catechol-O-methyltransferase: A revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 1995;34:4202–4210.
  13. Lachman HM, Papolos DF, Saito T, Yu Y-M, Szumlanski CL, Weinshilboum RM: Human catechol-O-methyltransferase pharmacogenetics: Description and a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996;6:243–250.
  14. Tenhunen J, Salminen M, Lundstrom K, Kiviluoto T, Savolainen R, Ulmanen I: Genomic organization of the human catechol-O-methyltransferase gene and its expression from two distinct promoters. Eur J Biochem 1994:223:1049–1054.
  15. Kunugi H, Nanko S, Ueki A, Otsuka E, Hattori M, Hoda F, Vallada HP, Arranz MJ, Collier DA: High and low activity alleles of catechol-O-methyltransferase gene: Ethnic difference and possible association with Parkinson’s disease. Neurosci Lett 1997;221:202–204.
  16. Hoda F, Nicholl D, Bennett P, Arran M, Aitchson KJ, al-Chalabi A, Kunugi A, Vallada H, Leigh PN, Cahundhuri KR: No association between Parkinson’s disease and low-activity alleles of catechol-O-methyltransferase. Biochem Biophys Res Commun 1996;228:780–784.
  17. Yoritaka A, Hattori N, Yoshino H, Mizuno Y: Catechol-O-methyltransferase genotype and susceptibility to Parkinson’s disease in Japan. J Neural Transm 1997;104:1313–1317.
  18. Mcleod HL, Fang L, Luo X, Scott EP, Evans W: Ethnic differences in erythrocyte catechol-O-methyltransferase activity in black and white Africans. J Pharmacol Exp Ther 1994;270:26–29.
  19. Cohen G: Monoamine oxidase, hydrogen peroxide, and Parkinson’s disease. Adv Neurol 1987;45:119–125.
  20. Da Prada M, Borgulya J, Napolitano A, Harfely WE: The pharmacology of Parkinson’s disease: Basic aspects and recent advances. Experientia (Basel) 1984;40:1165–1172.
  21. Männistö PT, Ulmanen I, Lundström K, Taskinen J, Tenhunen J, Tilgmann C, Kaakola S: Catechol-O-methyltransferase (COMT) and properties of selective COMT inhibitors. Prog Drug Res 1992;39:291–350.


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