title: 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.
authors: Center for Human Genetic Research, Massachusetts General Hospital, Simches Research Building, Room 5414, 185 Cambridge Street, Boston, MA, 02114, USA.
authors: Eliana Marisa
authors: EM
authors: Ramos
authors: Jeanne C
authors: JC
authors: Latourelle
authors: Tammy
authors: T
authors: Gillis
authors: Jayalakshmi S
authors: JS
authors: Mysore
authors: Ferdinando
authors: F
authors: Squitieri
authors: Alba
authors: A
authors: Di Pardo
authors: Stefano
authors: S
authors: Di Donato
authors: Cinzia
authors: C
authors: Gellera
authors: Michael R
authors: MR
authors: Hayden
authors: Patrick J
authors: PJ
authors: Morrison
authors: Martha
authors: M
authors: Nance
authors: Christopher A
authors: CA
authors: Ross
authors: Russell L
authors: RL
authors: Margolis
authors: Estrella
authors: E
authors: Gomez-Tortosa
authors: Carmen
authors: C
authors: Ayuso
authors: Oksana
authors: O
authors: Suchowersky
authors: Ronald J
authors: RJ
authors: Trent
authors: Elizabeth
authors: E
authors: McCusker
authors: Andrea
authors: A
authors: Novelletto
authors: Marina
authors: M
authors: Frontali
authors: Randi
authors: R
authors: Jones
authors: Tetsuo
authors: T
authors: Ashizawa
authors: Samuel
authors: S
authors: Frank
authors: Marie-Helene
authors: MH
authors: Saint-Hilaire
authors: Steven M
authors: SM
authors: Hersch
authors: Herminia D
authors: HD
authors: Rosas
authors: Diane
authors: D
authors: Lucente
authors: Madaline B
authors: MB
authors: Harrison
authors: Andrea
authors: A
authors: Zanko
authors: Ruth K
authors: RK
authors: Abramson
authors: Karen
authors: K
authors: Marder
authors: James F
authors: JF
authors: Gusella
authors: Jong-Min
authors: JM
authors: Lee
authors: Isabel
authors: I
authors: Alonso
authors: Jorge
authors: J
authors: Sequeiros
authors: Richard H
authors: RH
authors: Myers
authors: Marcy E
authors: ME
authors: Macdonald
mesh_terms: D017668:Age of Onset; D002394:Catechol O-Methyltransferase / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics*; D009434:Neural Pathways / Q000378:metabolism; D011110:Polymorphism, Genetic; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
chemical_list: D002394:Catechol O-Methyltransferase; D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D016194:Receptors, N-Methyl-D-Aspartate; C581293:DRD2 protein, human; C493599:DRD4 protein, human; C121001:NR2B NMDA receptor; C493214:SLC6A3 protein, human; C588010:COMT protein, human
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