title: Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease.
abstract: Pyridoxal-5-phosphate, the biological active form of pyridoxine, is a cofactor for dopa-decarboxylase (DDC) enzyme. Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain. However, this effect can be negated in the presence of a DDC inhibitor, which potentiates plasma levodopa level. A single nucleotide polymorphism at the nucleotide 1947 in the catechol-O-methyltransferase (COMT) gene encodes the high (COMT(H)) and low activity (COMT(L)) forms of the enzyme. In this study, we examined the effect of the COMT(L) allele on the clinical response to pyridoxine in Parkinson's disease (PD) patients. PD patients who were on stable and optimized dose of levodopa were included in this study. Their mean motor and activities of living score improved after high dose pyridoxine (P = 0.09, P = 0.04), and worsened after a washout period (P = 0.005, P = 0.001). Using a multivariate model, the presence of the COMT(L) allele predicted response to pyridoxine, with the best outcome observed in COMT(L/L) homozygotes. Our observational study suggests that the status the functional COMT(L) variant may be potentially useful to select PD patients for high dose pyridoxine therapy.
authors.affiliation: Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169608. gnrtek@sgh.com.sg
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
authors.forename: Sin-Yun
authors.initials: SY
authors.lastname: Cheah
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fook-Chong
authors.forename: Kenneth
authors.initials: K
authors.lastname: Yew
authors.forename: V R
authors.initials: VR
authors.lastname: Chandran
authors.forename: Sau-Ying
authors.initials: SY
authors.lastname: Lum
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yi
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D018592:Cross-Over Studies; D004296:Dopa Decarboxylase / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011597:Psychomotor Performance / Q000187:drug effects; D011736:Pyridoxine / Q000627:therapeutic use*; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D000978:Antiparkinson Agents; D014803:Vitamin B Complex; D007980:Levodopa; D002394:Catechol O-Methyltransferase; D004296:Dopa Decarboxylase; D011736:Pyridoxine