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 Louis Margolis, Estrella Gomez-Tortosa, Carmen Ayuso, Oksana Suchowersky, Ronald J. Trent, Elizabeth McCusker, Andrea Novelletto, Marina Frontali & 17 others Randi 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 journalArticle

Abstract

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
JournalNeurogenetics
Volume14
Issue number3-4
DOIs
StatePublished - 2013

Fingerprint

Huntington Disease
Minisatellite Repeats
N-Methyl-D-Aspartate Receptors
Genes
Dopamine
3' Untranslated Regions
Age of Onset
Neurodegenerative Diseases
Exons

Keywords

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

ASJC Scopus subject areas

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

Cite this

Ramos, E. M., Latourelle, J. C., Gillis, T., Mysore, J. S., Squitieri, F., Di Pardo, A., ... MacDonald, M. E. (2013). Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset. Neurogenetics, 14(3-4), 173-179. https://doi.org/10.1007/s10048-013-0364-y

Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset. / Ramos, Eliana Marisa; Latourelle, Jeanne C.; Gillis, Tammy; Mysore, Jayalakshmi S.; Squitieri, Ferdinando; Di Pardo, Alba; Di Donato, Stefano; Gellera, Cinzia; Hayden, Michael R.; Morrison, Patrick J.; Nance, Martha; Ross, Christopher A; Margolis, Russell Louis; Gomez-Tortosa, Estrella; Ayuso, Carmen; Suchowersky, Oksana; Trent, Ronald J.; McCusker, Elizabeth; Novelletto, Andrea; Frontali, Marina; Jones, Randi; Ashizawa, Tetsuo; Frank, Samuel; Saint-Hilaire, Marie Helene; Hersch, Steven M.; Rosas, Herminia D.; Lucente, Diane; Harrison, Madaline B.; Zanko, Andrea; Abramson, Ruth K.; Marder, Karen; Gusella, James F.; Lee, Jong Min; Alonso, Isabel; Sequeiros, Jorge; Myers, Richard H.; MacDonald, Marcy E.

In: Neurogenetics, Vol. 14, No. 3-4, 2013, p. 173-179.

Research output: Contribution to journalArticle

Ramos, EM, Latourelle, JC, Gillis, T, Mysore, JS, Squitieri, F, Di Pardo, A, Di Donato, S, Gellera, C, Hayden, MR, Morrison, PJ, Nance, M, Ross, CA, Margolis, RL, Gomez-Tortosa, E, Ayuso, C, Suchowersky, O, Trent, RJ, McCusker, E, Novelletto, A, Frontali, M, Jones, R, Ashizawa, T, Frank, S, Saint-Hilaire, MH, Hersch, SM, Rosas, HD, Lucente, D, Harrison, MB, Zanko, A, Abramson, RK, Marder, K, Gusella, JF, Lee, JM, Alonso, I, Sequeiros, J, Myers, RH & MacDonald, ME 2013, 'Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset', Neurogenetics, vol. 14, no. 3-4, pp. 173-179. https://doi.org/10.1007/s10048-013-0364-y
Ramos, Eliana Marisa ; Latourelle, Jeanne C. ; Gillis, Tammy ; Mysore, Jayalakshmi S. ; Squitieri, Ferdinando ; Di Pardo, Alba ; Di Donato, Stefano ; Gellera, Cinzia ; Hayden, Michael R. ; Morrison, Patrick J. ; Nance, Martha ; Ross, Christopher A ; Margolis, Russell Louis ; Gomez-Tortosa, Estrella ; Ayuso, Carmen ; Suchowersky, Oksana ; Trent, Ronald J. ; McCusker, Elizabeth ; Novelletto, Andrea ; Frontali, Marina ; Jones, Randi ; Ashizawa, Tetsuo ; Frank, Samuel ; Saint-Hilaire, Marie Helene ; Hersch, Steven M. ; Rosas, Herminia D. ; Lucente, Diane ; Harrison, Madaline B. ; Zanko, Andrea ; Abramson, Ruth K. ; Marder, Karen ; Gusella, James F. ; Lee, Jong Min ; Alonso, Isabel ; Sequeiros, Jorge ; Myers, Richard H. ; MacDonald, Marcy E. / Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset. In: Neurogenetics. 2013 ; Vol. 14, No. 3-4. pp. 173-179.
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abstract = "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.",
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T1 - Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset

AU - Ramos, Eliana Marisa

AU - Latourelle, Jeanne C.

AU - Gillis, Tammy

AU - Mysore, Jayalakshmi S.

AU - Squitieri, Ferdinando

AU - Di Pardo, Alba

AU - Di Donato, Stefano

AU - Gellera, Cinzia

AU - Hayden, Michael R.

AU - Morrison, Patrick J.

AU - Nance, Martha

AU - Ross, Christopher A

AU - Margolis, Russell Louis

AU - Gomez-Tortosa, Estrella

AU - Ayuso, Carmen

AU - Suchowersky, Oksana

AU - Trent, Ronald J.

AU - McCusker, Elizabeth

AU - Novelletto, Andrea

AU - Frontali, Marina

AU - Jones, Randi

AU - Ashizawa, Tetsuo

AU - Frank, Samuel

AU - Saint-Hilaire, Marie Helene

AU - Hersch, Steven M.

AU - Rosas, Herminia D.

AU - Lucente, Diane

AU - Harrison, Madaline B.

AU - Zanko, Andrea

AU - Abramson, Ruth K.

AU - Marder, Karen

AU - Gusella, James F.

AU - Lee, Jong Min

AU - Alonso, Isabel

AU - Sequeiros, Jorge

AU - Myers, Richard H.

AU - MacDonald, Marcy E.

PY - 2013

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N2 - 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.

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