Abstract
The expansion of a polymorphic CAG repeat in the HD gene encoding huntingtin has been identified as the major cause of Huntington’s disease (HD) and determines 42–73% of the variance in the age-at-onset of the disease. Polymorphisms in huntingtin interacting or associated genes are thought to modify the course of the disease. To identify genetic modifiers influencing the age at disease onset, we searched for polymorphic markers in the GRIK2, TBP, BDNF, HIP1 and ZDHHC17 genes and analysed seven of them by association studies in 980 independent European HD patients. Screening for unknown sequence variations we found besides several silent variations three polymorphisms in the ZDHHC17 gene. These and polymorphisms in the GRIK2, TBP and BDNF genes were analysed with respect to their association with the HD age-at-onset. Although some of the factors have been defined as genetic modifier factors in previous studies, none of the genes encoding GRIK2, TBP, BDNF and ZDHHC17 could be identified as a genetic modifier for HD.
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Acknowledgments
This study was supported by the GeNeMove Network for hereditary movement disorders financed by BMBF. SDD research was supported by a grant of the Italian Minister of Health “Malattie Neurodegenerative” 2004–2006. The Polish part of the study performed in the Department of Genetics, Institute of Psychiatry and Neurology was supported by the State Committee for Scientific Research PBZ-KBN-042/P05/2001. ANB’s research is sponsored by Bogazici University Research Funds and by Suna-Inan Kirac Foundation. The authors are grateful to Drs Marc Abramowicz and Pascale Cochaux from the Department of Molecular Genetics of Erasme Hospital, Brussels, Belgium, for their help.
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Metzger, S., Bauer, P., Tomiuk, J. et al. Genetic analysis of candidate genes modifying the age-at-onset in Huntington’s disease. Hum Genet 120, 285–292 (2006). https://doi.org/10.1007/s00439-006-0221-2
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DOI: https://doi.org/10.1007/s00439-006-0221-2