Lack of effect of polymorphisms in dopamine metabolism related genes on imaging of TRODAT-1 in striatum of asymptomatic volunteers and patients with Parkinson's disease

Mov Disord. 2003 Jul;18(7):804-12. doi: 10.1002/mds.10430.

Abstract

SPECT scanning using (99)Tc-TRODAT-1, a ligand that binds to dopamine transporters, may be useful for detection of early Parkinson's disease (PD), diagnosis of presymptomatic individuals, and monitoring disease progression. Understanding whether genetic factors contribute to inter-individual variability is crucial for interpreting imaging results in the context of disease pathophysiology. We tested whether polymorphisms in the genes for catechol-O-methyltransferase (COMT), monoamine-oxidase B (MAO-B), and the dopamine transporter (DAT) influence dopamine uptake parameters in the striatum in vivo in asymptomatic volunteers and patients with PD as measured with (99)Tc-TRODAT-1. (99)Tc-TRODAT-1 binding declined with age in both asymptomatic volunteers and PD patients, and depended on disease duration in PD patients. We found no significant association between COMT, MAO-B, and DAT polymorphisms and results of (99)Tc-TRODAT-1 testing in asymptomatic volunteers or patients with PD. In PD patients, the age of disease onset and speed of progression did not differ based on these polymorphisms. These results demonstrate that these specific genetic variations do not alter the fidelity of (99)Tc-TRODAT-1 as a measure of dopaminergic function in asymptomatic volunteer individuals or patients with PD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Catechol O-Methyltransferase / genetics
  • Corpus Striatum / diagnostic imaging*
  • Disease Progression
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Early Diagnosis
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Image Processing, Computer-Assisted*
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Minisatellite Repeats
  • Monoamine Oxidase / genetics
  • Nerve Tissue Proteins*
  • Organotechnetium Compounds*
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Radiopharmaceuticals*
  • Reference Values
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tomography, Emission-Computed, Single-Photon*
  • Tropanes*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • SLC6A3 protein, human
  • Tropanes
  • technetium Tc 99m TRODAT-1
  • Monoamine Oxidase
  • Catechol O-Methyltransferase
  • Dopamine