Publication:
Influence of single nucleotide polymorphisms in COMT, MAO-A and BDNF genes on dyskinesias and levodopa use in Parkinson’s disease

dc.contributor.author Cheshire, Perdita en_US
dc.contributor.author Bertram, Kelly en_US
dc.contributor.author Ling, Helen en_US
dc.contributor.author O'Sullivan, Sean S en_US
dc.contributor.author Halliday, Glenda en_US
dc.contributor.author McLean, Catriona en_US
dc.contributor.author Bras, Jose en_US
dc.contributor.author Foltynie, Tom en_US
dc.contributor.author Storey, Elsdon en_US
dc.contributor.author Williams, David R en_US
dc.date.accessioned 2021-11-25T12:29:34Z
dc.date.available 2021-11-25T12:29:34Z
dc.date.issued 2013 en_US
dc.description.abstract Background: Clinical heterogeneity in the development of levodopa-induced dyskinesias suggests endogenous factors play a significant role in determining their overall prevalence. We hypothesised that single nucleotide polymorphisms (SNPs) in specific genes may result in a clinical phenotype conducive to an increased risk of dyskinesia. Methods: We examined the influence of SNPs in the catechol O-methyltransferase (COMT), monoamine oxidase A (MAO-A) and brain-derived neurotrophic factor (BDNF) genes on time to onset and prevalence of dyskinesias in a cohort of 285 pathologically confirmed Parkinson’s disease patients. Results: Dyskinetic patients demonstrated younger age at disease onset (60.3 years vs. 66.4 years, p<0.0001), a longer disease duration (17.0 years vs. 12.0 years, p<0.0001) and a higher maximum daily levodopa equivalent dose (LED; 926.7 mg/day vs. 617.1 mg/day, p<0.0001) than patients without dyskinesias. No individual SNP was found to influence prevalence or time to onset of dyskinesias, including after adjustment for age at disease onset, disease duration, and maximum daily LED. We observed that patients carrying alleles conferring both high COMT activity and increased MAO-A mRNA expression received significantly higher maximum and mean daily LEDs than those with low enzyme activity/mRNA expression (max LED: 835mg ± 445mg vs. 508mg ± 316mg; p=0.0056, mean LED: 601mg ± 335mg vs. 398mg ± 260mg; p=0.025). Conclusions: Individual SNPs in BDNF, COMT and MAO-A genes did not influence prevalence or time to onset of dyskinesias in this cohort. The possibility that combined COMT and MAO-A genotype is a significant factor in determining an individual’s lifetime levodopa exposure warrants further investigation. en_US
dc.identifier.issn 1660-2854 en_US
dc.identifier.uri http://hdl.handle.net/1959.4/53639
dc.language English
dc.language.iso EN en_US
dc.rights CC BY-NC-ND 3.0 en_US
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/3.0/au/ en_US
dc.source Legacy MARC en_US
dc.subject.other catechol-O-methyltransferase (COMT) en_US
dc.subject.other Parkinson’s disease (PD) en_US
dc.subject.other levodopa-induced dyskinesias (LID) en_US
dc.subject.other brain-derived neurotrophic factor (BDNF) en_US
dc.subject.other monoamine-oxidase A (MAO-A) en_US
dc.title Influence of single nucleotide polymorphisms in COMT, MAO-A and BDNF genes on dyskinesias and levodopa use in Parkinson’s disease en_US
dc.type Journal Article en
dcterms.accessRights open access
dspace.entity.type Publication en_US
unsw.accessRights.uri https://purl.org/coar/access_right/c_abf2
unsw.identifier.doiPublisher http://dx.doi.org/10.1159/000351097 en_US
unsw.relation.faculty Medicine & Health
unsw.relation.ispartofissue 1 en_US
unsw.relation.ispartofjournal Neurodegenerative diseases en_US
unsw.relation.ispartofpagefrompageto 24-28 en_US
unsw.relation.ispartofvolume 13 en_US
unsw.relation.originalPublicationAffiliation Cheshire, Perdita, Department of Medicine (Neuroscience), Monash University (Alfred Hospital), Melbourne, Australia en_US
unsw.relation.originalPublicationAffiliation Bertram, Kelly, Neurology Department, Alfred Hospital, Melbourne, Australia en_US
unsw.relation.originalPublicationAffiliation Ling, Helen, Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, University College London, London, UK 4 Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK en_US
unsw.relation.originalPublicationAffiliation O'Sullivan, Sean S, Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK 5 Cork University Hospital Neurosciences Department, Cork, Ireland en_US
unsw.relation.originalPublicationAffiliation Halliday, Glenda, Neuroscience Research Australia, Faculty of Medicine, UNSW en_US
unsw.relation.originalPublicationAffiliation McLean, Catriona, Anatomical Pathology, Alfred Hospital, Melbourne, Australia en_US
unsw.relation.originalPublicationAffiliation Bras, Jose, Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK en_US
unsw.relation.originalPublicationAffiliation Foltynie, Tom, Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, UK en_US
unsw.relation.originalPublicationAffiliation Storey, Elsdon, Department of Medicine (Neuroscience), Monash University (Alfred Hospital), Melbourne, Australia 2 Neurology Department, Alfred Hospital, Melbourne, Australia en_US
unsw.relation.originalPublicationAffiliation Williams, David R, Department of Medicine (Neuroscience), Monash University (Alfred Hospital), Melbourne, Australia 2 Neurology Department, Alfred Hospital, Melbourne, Australia en_US
unsw.relation.school Neuroscience Research Australia *
unsw.subject.fieldofresearchcode 110903 Central Nervous System en_US
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