TY - JOUR
T1 - TAA repeat variation in the GRIK2 gene does not influence age at onset in Huntington's disease
AU - Lee, Ji Hyun
AU - Lee, Jong Min
AU - Ramos, Eliana Marisa
AU - Gillis, Tammy
AU - Mysore, Jayalakshmi S.
AU - Kishikawa, Shotaro
AU - Hadzi, Tiffany
AU - Hendricks, Audrey E.
AU - Hayden, Michael R.
AU - Morrison, Patrick J.
AU - Nance, Martha
AU - Ross, Christopher A.
AU - Margolis, Russell L.
AU - Squitieri, Ferdinando
AU - Gellera, Cinzia
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 - Sequeiros, Jorge
AU - Bernhard Landwehrmeyer, G.
AU - Shoulson, Ira
AU - Myers, Richard H.
AU - MacDonald, Marcy E.
AU - Gusella, James F.
N1 - Funding Information:
The authors thank contributors to the HD-MAPS, COHORT and Registry studies, listed in Appendix 1. This work was supported by grants from the National Institutes of Health NINDS Huntington’s Disease Center Without Walls NS16367, the CHDI Foundation Inc., and the Huntington’s Disease Society of America’s Coalition for the Cure. JHL received support from a National Research Foundation of Korea Grant funded by the Korean Government [NRF-2009-352-E00010]. EMR is the recipient of a scholarship from FCT (SFRH/BD/44335/2008). The Huntington Study Group COHORT project was supported by the CHDI Foundation, Inc. and the REGISTRY study of the European Huntington’s Disease Network was supported by the High Q Foundation.
PY - 2012/8/3
Y1 - 2012/8/3
N2 - 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.
AB - 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.
KW - Age at onset
KW - GRIK2
KW - Genetic modifier
KW - Huntington's disease (HD)
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U2 - 10.1016/j.bbrc.2012.06.120
DO - 10.1016/j.bbrc.2012.06.120
M3 - Article
C2 - 22771793
AN - SCOPUS:84864757021
SN - 0006-291X
VL - 424
SP - 404
EP - 408
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -