Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset

Eliana Marisa Ramos, Jeanne C. Latourelle, Tammy Gillis, Jayalakshmi S. Mysore, Ferdinando Squitieri, Alba Di Pardo, Stefano Di Donato, Cinzia Gellera, Michael R. Hayden, Patrick J. Morrison, Martha Nance, Christopher A. Ross, Russell L. Margolis, Estrella Gomez-Tortosa, Carmen Ayuso, Oksana Suchowersky, Ronald J. Trent, Elizabeth McCusker, Andrea Novelletto, Marina FrontaliRandi Jones, Tetsuo Ashizawa, Samuel Frank, Marie Helene Saint-Hilaire, Steven M. Hersch, Herminia D. Rosas, Diane Lucente, Madaline B. Harrison, Andrea Zanko, Ruth K. Abramson, Karen Marder, James F. Gusella, Jong Min Lee, Isabel Alonso, Jorge Sequeiros, Richard H. Myers, Marcy E. MacDonald

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. It is caused by the expansion of the HTT CAG repeat, which is the major determinant of age at onset (AO) of motor symptoms. Aberrant function of N-methyl-D-aspartate receptors and/or overexposure to dopamine has been suggested to cause significant neurotoxicity, contributing to HD pathogenesis. We used genetic association analysis in 1,628 HD patients to evaluate candidate polymorphisms in N-methyl-D-aspartate receptor subtype genes (GRIN2A rs4998386 and rs2650427, and GRIN2B rs1806201) and functional polymorphisms in genes in the dopamine pathway (DAT1 3′ UTR 40-bp variable number tandem repeat (VNTR), DRD4 exon 3 48-bp VNTR, DRD2 rs1800497, and COMT rs4608) as potential modifiers of the disease process. None of the seven polymorphisms tested was found to be associated with significant modification of motor AO, either in a dominant or additive model, after adjusting for ancestry. The results of this candidate-genetic study therefore do not provide strong evidence to support a modulatory role for these variations within glutamatergic and dopaminergic genes in the AO of HD motor manifestations.

Original languageEnglish (US)
Pages (from-to)173-179
Number of pages7
Issue number3-4
StatePublished - Nov 2013


  • Dopamine pathway
  • Genetic modifiers
  • Glutamate receptors
  • Huntington's disease

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience


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