Dopaminergic denervation severity depends on COMT Val158Met polymorphism in Parkinson's disease.

Müllner, Julia; Gharrad, Iman; Habert, Marie-Odile; Kas, Aurélie; Martini, Jean-Baptiste; Cormier-Dequaire, Florence; Tahiri, Khadija; Vidailhet, Marie; Meier, Niklaus; Brice, Alexis; Schüpbach, Michael; Mallet, Alain; Hartmann, Andreas; Corvol, Jean-Christophe (2015). Dopaminergic denervation severity depends on COMT Val158Met polymorphism in Parkinson's disease. Parkinsonism & related disorders, 21(5), pp. 471-476. Elsevier 10.1016/j.parkreldis.2015.02.009

[img] Text
Dopaminergic denervation severity.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (296kB) | Request a copy

BACKGROUND Catecholamine-O-methyl-tranferase (COMT) initiates dopamine degradation. Its activity is mainly determined by a single nucleotide polymorphism in the COMT gene (Val158Met, rs4680) separating high (Val/Val, COMT(HH)), intermediate (Val/Met, COMT(HL)) and low metabolizers (Met/Met, COMT(LL)). We investigated dopaminergic denervation in the striatum in PD patients according to COMT rs4680 genotype. METHODS Patients with idiopathic PD were assessed for motor severity (UPDRS-III rating scale in OFF-state), dopaminergic denervation using [123I]-FP-CIT SPECT imaging, and genotyped for the COMT rs4680 enzyme. [123I]-FP-CIT binding potential (BP) for each voxel was defined by the ratio of tracer-binding in the region of interest (striatum, caudate nucleus and putamen) to that in a region of non-specific activity. Genotyping was performed using TaqMan(®) SNP genotyping assay. We used a regression model to evaluate the effect of COMT genotype on the BP in the striatum and its sub-regions. RESULTS Genotype distribution was: 11 (27.5%) COMT(HH), 26 (65%) COMT(HL) and 3 (7.5%) COMT(LL). There were no significant differences in disease severity, treatments, or motor scores between genotypes. When adjusted to clinical severity, gender and age, low and intermediate metabolizers showed significantly higher rates of striatal denervation (COMT(HL+LL) BP = 1.32 ± 0.04) than high metabolizers (COMT(HH), BP = 1.6 ± 0.08; F(1.34) = 9.0, p = 0.005). Striatal sub-regions showed similar results. BP and UPDRS-III motor scores (r = 0.44, p = 0.04) (p < 0.001) were highly correlated. There was a gender effect, but no gender-genotype interaction. CONCLUSIONS Striatal denervation differs according to COMT-Val158Met polymorphism. COMT activity may play a role as a compensatory mechanism in PD motor symptoms.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Müllner, Julia Nicole Maria; Meier, Niklaus and Schüpbach, Michael

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1353-8020

Publisher:

Elsevier

Language:

English

Submitter:

Romina Theiler

Date Deposited:

02 May 2016 10:14

Last Modified:

12 Sep 2017 06:17

Publisher DOI:

10.1016/j.parkreldis.2015.02.009

PubMed ID:

25753458

Uncontrolled Keywords:

COMT, Compensatory mechanism, Dopaminergic denervation, Motor symptoms, Parkinson's disease

BORIS DOI:

10.7892/boris.81584

URI:

https://boris.unibe.ch/id/eprint/81584

Actions (login required)

Edit item Edit item
Provide Feedback