PMID- 24008922
OWN - NLM
STAT- MEDLINE
DCOM- 20140806
LR  - 20220321
IS  - 1660-2862 (Electronic)
IS  - 1660-2854 (Print)
IS  - 1660-2854 (Linking)
VI  - 13
IP  - 1
DP  - 2014
TI  - Influence of single nucleotide polymorphisms in COMT, MAO-A and BDNF genes on 
      dyskinesias and levodopa use in Parkinson's disease.
PG  - 24-8
LID - 10.1159/000351097 [doi]
AB  - BACKGROUND: Clinical heterogeneity in the development of levodopa-induced 
      dyskinesias (LID) suggests endogenous factors play a significant role in 
      determining their overall prevalence. OBJECTIVE: We hypothesised that single 
      nucleotide polymorphisms (SNPs) in specific genes may result in a clinical 
      phenotype conducive to an increased risk of LID. 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 LID in a cohort of 
      285 pathologically confirmed Parkinson's disease patients, using data from their 
      complete disease course. RESULTS: Dyskinetic patients demonstrated younger age at 
      disease onset (60.3 vs. 66.4 years, p < 0.0001), a longer disease duration (17.0 
      vs. 12.0 years, p < 0.0001) and a higher maximum daily levodopa equivalent dose 
      (LED; 926.7 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 known risk factors. 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: 835 +/- 445 vs. 508 +/- 316 mg; p 
      = 0.0056, mean LED: 601 +/- 335 vs. 398 +/- 260 mg; 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.
CI  - Copyright (c) 2013 S. Karger AG, Basel.
FAU - Cheshire, Perdita
AU  - Cheshire P
AD  - Department of Medicine (Neuroscience), Monash University (Alfred Hospital), 
      Melbourne, Vic., Australia.
FAU - Bertram, Kelly
AU  - Bertram K
FAU - Ling, Helen
AU  - Ling H
FAU - O'Sullivan, Sean S
AU  - O'Sullivan SS
FAU - Halliday, Glenda
AU  - Halliday G
FAU - McLean, Catriona
AU  - McLean C
FAU - Bras, Jose
AU  - Bras J
FAU - Foltynie, Tom
AU  - Foltynie T
FAU - Storey, Elsdon
AU  - Storey E
FAU - Williams, David R
AU  - Williams DR
LA  - eng
GR  - 083948/WT_/Wellcome Trust/United Kingdom
GR  - WTCCC2/WT_/Wellcome Trust/United Kingdom
GR  - 084747/WT_/Wellcome Trust/United Kingdom
GR  - DH_/Department of Health/United Kingdom
GR  - 089698/Wellcome Trust/United Kingdom
GR  - MC_G1000735/MRC_/Medical Research Council/United Kingdom
GR  - R24 AA012725/AA/NIAAA NIH HHS/United States
GR  - K-0901/PUK_/Parkinson's UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130905
PL  - Switzerland
TA  - Neurodegener Dis
JT  - Neuro-degenerative diseases
JID - 101189034
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 46627O600J (Levodopa)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
RN  - EC 1.4.3.4. (monoamine oxidase A, human)
RN  - EC 2.1.1.6 (COMT protein, human)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
SB  - IM
MH  - Aged
MH  - Antiparkinson Agents/*administration & dosage/therapeutic use
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Catechol O-Methyltransferase/genetics
MH  - Cohort Studies
MH  - Dyskinesia, Drug-Induced/epidemiology/*genetics
MH  - Female
MH  - Humans
MH  - Levodopa/*adverse effects/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Monoamine Oxidase/genetics
MH  - Parkinson Disease/drug therapy/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Prevalence
MH  - Time Factors
PMC - PMC4194629
MID - EMS55215
OID - NLM: EMS55215
EDAT- 2013/09/07 06:00
MHDA- 2014/08/07 06:00
PMCR- 2014/10/13
CRDT- 2013/09/07 06:00
PHST- 2013/02/14 00:00 [received]
PHST- 2013/03/29 00:00 [accepted]
PHST- 2013/09/07 06:00 [entrez]
PHST- 2013/09/07 06:00 [pubmed]
PHST- 2014/08/07 06:00 [medline]
PHST- 2014/10/13 00:00 [pmc-release]
AID - 000351097 [pii]
AID - 10.1159/000351097 [doi]
PST - ppublish
SO  - Neurodegener Dis. 2014;13(1):24-8. doi: 10.1159/000351097. Epub 2013 Sep 5.