title: No association between Parkinson's disease and low-activity alleles of catechol O-methyltransferase.
abstract: Idiopathic Parkinson's disease (IPD) is characterised by the loss of pigmented neurones in the substantia nigra, leading to reduced tyrosine hydroxylase activity and depletion of dopamine. Treatments attempt to correct this deficit by the use of levodopa and inhibitors of dopamine metabolising enzymes such as catechol-O-methytransferase (COMT). A common amino-acid polymorphism in COMT, valine-108-methionine, results in a low activity form of the enzyme which we hypothesised may influence susceptibility to IPD. We examined this polymorphism in 139 Caucasian subjects with IPD and 173 control subjects, using a PCR-RFLP and a novel Amplification Refractory Mutation System (ARMS) assay. Allele and genotype frequencies were similar in the affected and control subjects, indicating that variation of COMT activity is not an aetiological factor in IPD. We have also characterised a new polymorphism, 256C/G, which is not associated with IPD. However it remains possible that allelic variation in COMT influences severity, type of pathology or treatment response to levodopa or COMT inhibitors.
authors.affiliation: Section of Molecular Genetics, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, United Kingdom.
authors.forename: F
authors.initials: F
authors.lastname: Hoda
authors.forename: D
authors.initials: D
authors.lastname: Nicholl
authors.forename: P
authors.initials: P
authors.lastname: Bennett
authors.forename: M
authors.initials: M
authors.lastname: Arranz
authors.forename: K J
authors.initials: KJ
authors.lastname: Aitchison
authors.forename: A
authors.initials: A
authors.lastname: al-Chalabi
authors.forename: H
authors.initials: H
authors.lastname: Kunugi
authors.forename: H
authors.initials: H
authors.lastname: Vallada
authors.forename: P N
authors.initials: PN
authors.lastname: Leigh
authors.forename: K R
authors.initials: KR
authors.lastname: Chaudhuri
authors.forename: D A
authors.initials: DA
authors.lastname: Collier
mesh_terms: D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D002394:Catechol O-Methyltransferase; D004298:Dopamine