Dataset Information

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

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.

SUBMITTER: Ramos EM

PROVIDER: S-EPMC3825533 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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

Ramos Eliana Marisa EM Latourelle Jeanne C JC Gillis Tammy T Mysore Jayalakshmi S JS Squitieri Ferdinando F Di Pardo Alba A Di Donato Stefano S Gellera Cinzia C Hayden Michael R MR Morrison Patrick J PJ Nance Martha M Ross Christopher A CA Margolis Russell L RL Gomez-Tortosa Estrella E Ayuso Carmen C Suchowersky Oksana O Trent Ronald J RJ McCusker Elizabeth E Novelletto Andrea A Frontali Marina M Jones Randi R Ashizawa Tetsuo T Frank Samuel S Saint-Hilaire Marie-Helene MH Hersch Steven M SM Rosas Herminia D HD Lucente Diane D Harrison Madaline B MB Zanko Andrea A Abramson Ruth K RK Marder Karen K Gusella James F JF Lee Jong-Min JM Alonso Isabel I Sequeiros Jorge J Myers Richard H RH Macdonald Marcy E ME

Neurogenetics 20130504 3-4

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 po ...[more]

PMID: 23644918

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Dataset Information

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

Publications

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

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