title: TAA repeat variation in the GRIK2 gene does not influence age at onset in Huntington's disease.
abstract: Huntington's disease is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat whose length is the major determinant of age at onset but remaining variation appears to be due in part to the effect of genetic modifiers. GRIK2, which encodes GluR6, a mediator of excitatory neurotransmission in the brain, has been suggested in several studies to be a modifier gene based upon a 3' untranslated region TAA trinucleotide repeat polymorphism. Prior to investing in detailed studies of the functional impact of this polymorphism, we sought to confirm its effect on age at onset in a much larger dataset than in previous investigations. We genotyped the HD CAG repeat and the GRIK2 TAA repeat in DNA samples from 2,911 Huntington's disease subjects with known age at onset, and tested for a potential modifier effect of GRIK2 using a variety of statistical approaches. Unlike previous reports, we detected no evidence of an influence of the GRIK2 TAA repeat polymorphism on age at motor onset. Similarly, the GRIK2 polymorphism did not show significant modifier effect on psychiatric and cognitive age at onset in HD. Comprehensive analytical methods applied to a much larger sample than in previous studies do not support a role for GRIK2 as a genetic modifier of age at onset of clinical symptoms in Huntington's disease.
authors: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA. jihyni@yuhs.ac
authors: Ji-Hyun
authors: JH
authors: Lee
authors: Jong-Min
authors: JM
authors: Lee
authors: Eliana Marisa
authors: EM
authors: Ramos
authors: Tammy
authors: T
authors: Gillis
authors: Jayalakshmi S
authors: JS
authors: Mysore
authors: Shotaro
authors: S
authors: Kishikawa
authors: Tiffany
authors: T
authors: Hadzi
authors: Audrey E
authors: AE
authors: Hendricks
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: Ferdinando
authors: F
authors: Squitieri
authors: Cinzia
authors: C
authors: Gellera
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: Jorge
authors: J
authors: Sequeiros
authors: G Bernhard
authors: GB
authors: Landwehrmeyer
authors: Ira
authors: I
authors: Shoulson
authors: Richard H
authors: RH
authors: Myers
authors: Marcy E
authors: ME
authors: MacDonald
authors: James F
authors: JF
authors: Gusella
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D018388:Codon, Terminator / Q000235:genetics*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018092:Kainic Acid Receptors / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*; D055815:Young Adult; D000097806:GluK2 Kainate Receptor
chemical_list: D020413:3' Untranslated Regions; D018388:Codon, Terminator; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor