Association Between Catechol-O-Methyltransferase (COMT) Gene Polymorphisms, Parkinson’s Disease, and Levodopa Efficacy
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Subjects and Methods
Patients (N = 97) with primary PD and healthy volunteers (N = 102) were recruited. Disease severity was assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn & Yahr grade at ‘On stage’. Genomic DNA was extracted from blood cells. Polymerase chain reaction and sequencing were used to detect COMT mutations. Data were analyzed by SPSS 18.0. False discovery rate (FDR) or Bonferroni correction was used if the result showed P < 0.05.
Four COMT mutations were detected in 199 subjects: rs74745580 (only in two patients with primary PD), rs4633, rs6267, and rs3838146. There were no statistical differences in frequencies of rs4633, rs6267, and rs3838146 genotypes between PD patients and the control group. The frequency of allele rs4633T was higher in PD patients than in the control group. UPDRS score was lower in rs4633 (CT/TT) carriers and rs3838146 (–C/– –) carriers than in rs4633 (CC) and rs3838146 (CC) carriers. PD patients carrying rs6267 (GT/TT) had higher UPDRS scores than patients with rs6267 (GG) (P < 0.05). The frequencies of the three polymorphisms were not statistically different between patients who did and did not receive l-Dopa; dose and duration of l-Dopa treatment did not differ between genotypes; and there was also no difference in the ratios of loss of efficacy towards levodopa.
The polymorphisms rs4633, rs6267, and rs3838146 were associated with severity of PD but were not associated with l-Dopa medication.
- Schrag, A, Quinn, N (2000) Dyskinesias and motor fluctuations in Parkinson’s disease. A community-based study. Brain 123: pp. 2297-2305 CrossRef
- Garcia Ruiz PJ, Meseguer E, Del Val J, et al. Motor complications in Parkinson disease: a prospective follow-up study. Clin Neuropharmacol. 2004;27(2):49–52.
- Hauser, RA, McDermott, MP, Messing, S (2006) Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease. Arch Neurol 63: pp. 1756-1760 CrossRef
- Thanvi, BR, Lo, TC (2004) Long term motor complications of levodopa: clinical features, mechanisms and management strategies. Postgrad Med J 80: pp. 452-458 CrossRef
- Woitalla, D, Karwasz, R, Müller, T (2000) The activity of catechol-O-methyltransferase in parkinsonian patients with “on–off fluctuations”. J Neural Transm 107: pp. 105-111 CrossRef
- Poewe WH, Deuschl G, Gordin A, et al., Celomen Study Group. Efficacy and safety of entacapone in Parkinson’s disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). Acta Neurol Scand. 2002;105:245–55.
- Poulopoulos, M, Waters, C (2010) Carbidopa/levodopa/entacapone: the evidence for its place in the treatment of Parkinson’s disease. Core Evid 27: pp. 1-10
- Hamaue, N, Ogata, A, Terado, M (2010) Entacapone, a catechol-O-methyltransferase inhibitor, improves the motor activity and dopamine content of basal ganglia in a rat model of Parkinson’s disease induced by Japanese encephalitis virus. Brain Res 14: pp. 110-115 CrossRef
- Bray, NJ, Buckland, PR, Williams, NM (2003) A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain. Am J Hum Genet 73: pp. 152-161 CrossRef
- Kimchi-Sarfaty, C, Oh, JM, Kim, IW (2007) A silent polymorphism in the MDR1 gene changes substrate specificity. Science 315: pp. 525-528 CrossRef
- Tai, CH, Wu, RM (2002) Catechol-O-methyltransferase and Parkinson’s disease. Acta Med Okayama 56: pp. 1-6
- Bialecka, M, Kurzawski, M, Klodowska-Duda, G (2008) The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinson’s disease, levodopa treatment response, and complications. Pharmacogenet Genomics 18: pp. 815-821 CrossRef
- Kalinderi, K, Fidani, L, Kourtesi, G (2008) No association of the Val158Met COMT polymorphism with Parkinson’s disease in the Greek population. Eur J Neurol 15: pp. e83 CrossRef
- Hoda, F, Nicholl, D, Bennett, P (1996) No association between Parkinson’s disease and low-activity alleles of catechol O-methyltransferase. Biochem Biophys Res Commun 228: pp. 780-784 CrossRef
- Williams-Gray, CH, Hampshire, A, Barker, RA (2008) Attentional control in Parkinson’s disease is dependent on COMT val 158 met genotype. Brain 131: pp. 397-408 CrossRef
- Wu, K, O’Keeffe, D, Politis, M (2012) The catechol-O-methyltransferase Val(158)Met polymorphism modulates fronto-cortical dopamine turnover in early Parkinson’s disease: a PET study. Brain 135: pp. 2449-2457 CrossRef
- Lau, LM, Verbaan, D, Marinus, J (2012) Catechol-O-methyltransferase Val158Met and the risk of dyskinesias in Parkinson’s disease. Mov Disord 27: pp. 132-135 CrossRef
- Antonini, A, Martinez-Martin, P, Chaudhuri, RK (2011) Wearing-off scales in Parkinson’s disease: critique and recommendations. Mov Disord 26: pp. 2169-2175 CrossRef
- Warren Olanow C, Kieburtz K, Rascol O, et al., Stalevo Reduction in Dyskinesia Evaluation in Parkinson’s Disease (STRIDE-PD) Investigators. Factors predictive of the development of levodopa-induced dyskinesia and wearing-off in Parkinson’s disease. Mov Disord. 2013;28(8):1064–71.
- Kunugi, H, Nanko, S, Ueki, A (1997) High and low activity alleles of catechol-O-methyltransferase gene: ethnic difference and possible association with Parkinson’s disease. Neurosci Lett 221: pp. 202-204 CrossRef
- Białecka, M, Kurzawski, M, Roszmann, A (2012) Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson’s disease. Pharmacogenet Genomics 22: pp. 716-724 CrossRef
- Nackley, AG, Shabalina, SA, Lambert, JE (2009) Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs. PLoS One 4: pp. e5237 CrossRef
- Białecka, M, Droździk, M, Kłodowska-Duda, G (2004) The effect of monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) polymorphisms on levodopa therapy in patients with sporadic Parkinson’s disease. Acta Neurol Scand 110: pp. 260-266 CrossRef
- Corvol, JC, Bonnet, C, Charbonnier-Beaupel, F (2011) The COMT Val158Met polymorphism affects the response to entacapone in Parkinson’s disease: a randomized crossover clinical trial. Ann Neurol. 69: pp. 111-118 CrossRef
- Watanabe, M, Harada, S, Nakamura, T (2003) Association between catechol-O-methyltransferase gene polymorphisms and wearing-off and dyskinesia in Parkinson’s disease. Neuropsychobiology 48: pp. 190-193 CrossRef
- Chong DJ, Suchowersky O, Szumlanski C, et al. The relationship between COMT genotype and the clinical effectiveness of tolcapone, a COMT inhibitor, in patients with Parkinson’s disease. Clin Neuropharmacol. 2000;23(3):143–8.
- Contin, M, Martinelli, P, Mochi, M (2005) Genetic polymorphism of catechol-O-methyltransferase and levodopa pharmacokinetic–pharmacodynamic pattern in patients with Parkinson’s disease. Mov Disord 20: pp. 734-739 CrossRef
- Lee, MS, Lyoo, CH, Ulmanen, I (2001) Genotypes of catechol-O-methyltransferase and response to levodopa treatment in patients with Parkinson’s disease. Neurosci Lett 298: pp. 131-134 CrossRef
- Association Between Catechol-O-Methyltransferase (COMT) Gene Polymorphisms, Parkinson’s Disease, and Levodopa Efficacy
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