Abstract Details

Title Functional MAOB Gene Intron 13 Polymorphism Predicts Levodopa-induced Dyskinesia in Parkinson’s Disease

Topic Movement Disorders

Presentation(s) S53 - Movement Disorders: Genetics and Clinical Features (4:25 PM-4:36 PM)

Poster/Presentation
Number 006

Background PD is associated with motor complications, such as wearing-off and levodopa-induced dyskinesia (LID), in about 50% of patients after 5 years of treatment, which can significantly impair quality of life in affected patients. It has been hypothesized that functional gene polymorphisms encoding enzyme activity in the catabolic enzymes dopa-carboxylase (DDC), monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) and dopamine transporter (DAT) activity might modulate the individual risk for levodopa-induced motor complications.

Objective To investigate the predictive value of common functional gene polymorphisms in dopamine metabolism for the onset of motor complications in Parkinson's disease (PD).

Design/Methods

Retrospective, observer-blinded, long-term cohort study of 28 PD patients who underwent genotyping of DDC (rs921451), MAOB (rs1799836), COMT (rs4680) and dopamine transporter/solute carrier family 6 member 3 (DAT/SLC6A3, variable number tandem repeats) polymorphisms and meticulous clinical follow-up from 2005 through 2018. Onset of wearing-off and LID was determined by blinded clinical assessments. Predictive values of genotypes for motor complications were evaluated using Cox proportional hazard models.

Results During a median follow-up time of 11 years, 23 (77%) patients developed wearing-off, 16 (53%) dyskinesias, and 23 (77%) any motor complication. Univariate and multivariate Cox regression analysis adjusting for relevant covariates revealed that the MAOB (rs1799836) polymorphism predicted development of LID with the MAOB^CC/(C)/CT genotype (resulting in low/intermediate brain enzyme activity) being associated with lower risk for LID development than the MAOB^TT/(T) genotype (unadjusted HR 0.264, 95% CI .089 to .787, P=.012; adjusted HR 0.142, 95% CI .039 to .520, P=.003). In contrast, functional polymorphisms in DDC (rs921451), COMT (rs4680) and DAT (VNTR) polymorphisms were not predictive of motor complications.

Conclusions The MAOB (rs1799836) polymorphism predicts LID in PD potentially by modifying compensatory changes in dopamine metabolism. Early assessment of the genotype in this polymorphism might be helpful to stratify PD patients with respect to their individual risk for LID.

Authors/Disclosures
Alexander Storch, MD (University Medical Center Rostock) PRESENTER	No disclosure on file
Matthias Lohle	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Heinz Reichmann, MD, FAAN (Dept. Neurology)	Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zambon. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zambon. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyowa. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bial. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zambon. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Thieme. Dr. Reichmann has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wissenschaftsverlag.
	No disclosure on file
Jean Christophe Corvol, MD (GH Pitie Salpetriere)	No disclosure on file

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