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A single nucleotide polymorphism in the coding region of PGC-1α is a male-specific modifier of Huntington disease age-at-onset in a large European cohort
Open accessAbstract
BACKGROUND: Genetic modifiers are important clues for the identification of therapeutic targets in neurodegenerative diseases. Huntington disease (HD) is one of the most common autosomal dominant inherited neurodegenerative diseases. The clinical symptoms include motor abnormalities, cognitive decline and behavioral disturbances. Symptom onset is typically between 40 and 50 years of age, but can vary by several decades in extreme cases and this is in part determined by modifying genetic factors. The metabolic master regulator PGC-1α, coded by the PPARGC1A gene, coordinates cellular respiration and was shown to play a role in neurodegenerative diseases, including HD. METHODS: Using a candidate gene approach we analyzed a large European cohort (n = 1706) from the REGISTRY study for associations between PPARGC1A genotype and age at onset (AO) in HD. RESULTS: We report that a coding variant (rs3736265) in PPARGC1A is associated with an earlier motor AO in men but not women carrying the HD mutation. CONCLUSIONS: These results further strengthen the evidence for a role of PGC-1α in HD and unexpectedly suggest a gender effect.
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Metadata
- Authors
- For the European Huntington Disease Network, Weydt, P., Soyal, S. M., Landwehrmeyer, G. B., & Patsch, W.
- Affiliations
- Universität Ulm (DE)
- Paracelsus Medical University (AT)
- Corresponding author
- Weydt, Patrick
- Venue
- BMC Neurology
- Published
- 2014-01-02
- Volume
- 14
- Issue
- 1
- Pages
- 1-1
- ISSN
- 1471-2377 (ISSN-L)
- PMC
- PMC3880172
- OpenAlex
- W1990817194
- Cited by
- 206
- References
- 36
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 8 · 2023: 8 · 2022: 4 · 2021: 50 · 2020: 25 · 2019: 13 · 2018: 24 · 2017: 29 · 2016: 21 · 2015: 5 · 2014: 8
- FWCI
- 9.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- European Huntington's Disease Network
- Austrian Science Fund (P 19893)
- Deutsches Zentrum für Neurodegenerative Erkrankungen
- Paracelsus Medizinische Privatuniversität
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- Huntington's disease, PGC-1α, single nucleotide polymorphisms, age of onset, genetic modifiers, sex differences, motor symptoms, neurodegeneration, candidate gene association
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Europe, Female, Humans, Huntington Disease, Male, Registries, Transcription Factors, Cohort Studies, Open Reading Frames, Age of Onset, Polymorphism, Single Nucleotide
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