Association of age at onset in Huntington disease with functional promoter variations in NPY and NPY2R
| العنوان: | Association of age at onset in Huntington disease with functional promoter variations in NPY and NPY2R |
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| المؤلفون: | Jörg T. Epplen, Eugen Kloster, Larissa Arning, Denis A. Akkad, Carsten Saft |
| المصدر: | Journal of Molecular Medicine. 92:177-184 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Huntingtin, Genotype, Cell Survival, Nerve Tissue Proteins, Single-nucleotide polymorphism, Biology, medicine.disease_cause, PC12 Cells, Polymorphism, Single Nucleotide, Cohort Studies, Exon, Gene Frequency, Cell Line, Tumor, Germany, mental disorders, Drug Discovery, Genetic variation, medicine, Huntingtin Protein, Animals, Humans, Neuropeptide Y, Age of Onset, Promoter Regions, Genetic, Receptor, Genetics (clinical), Genetics, Mutation, Exons, Neuropeptide Y receptor, Peptide Fragments, Rats, Receptors, Neuropeptide Y, Huntington Disease, Molecular Medicine |
| الوصف: | Huntington disease (HD) is caused by the expansion of a CAG repeat within exon 1 of the HTT gene. Although the variation in age at onset (AO) is partly explained by the lengths of the expanded repeats, the unexplained variation is highly heritable, emphasizing the role of the so-called genetic background on disease expression. Neuropeptide Y (NPY) has been implicated in the modulation of neuroprotection, neurogenesis, and neuroinflammation. Therefore, the aim of the present study was to analyze different single nucleotide polymorphisms (SNPs) in order to test the possibility that genetic variation in NPY or three of its receptor genes (NPY1R, NPY2R, and NPY5R) may explain some of the variation in AO of HD motor manifestations, in a comprehensive cohort of 487 German HD patients. We found modest association of the AO with two NPY promoter variations and a highly significant association with a NPY2R promoter SNP (rs2234759; p = 0.0004). Investigating the functional impact of rs2234759 by luciferase assays revealed that the high-expression NPY2R genotypes were associated with later AO in HD. Additionally, treatment of PC12 cells expressing mutant huntingtin (htt) exon 1 with NPY and the NPY2R agonist NPY(3-36) has a protective effect against mutant htt-induced cell death. Thus, NPY might act through Y2 receptors to slow down the course of HD, and hence, this peptide could be of interest as a possible therapeutic agent. |
| تدمد: | 1432-1440 0946-2716 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75208f6b17df0ea488053bea7ed3e1e8Test https://doi.org/10.1007/s00109-013-1092-3Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....75208f6b17df0ea488053bea7ed3e1e8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321440 09462716 |
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