Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington’s disease

Neurobiology of Disease

卷:24

James F. Gusella¹  Marcy E. MacDonald¹  Michael Hayden²  Simon Warby²  Jian-Liang Li³  Michael M. Hakky⁴  Richard H. Myers⁴  Tammy Gillis⁴  Shotaro Kishikawa⁴ 

[1] Huntington’s Disease Society of America Coalition for the Cure Team 5: Huntingtin Normal Function, USA;

[2] Centre for Molecular Medicine and Therapeutics and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada;

[3] Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA;

[4] Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA;

关键词: Huntington’s disease (HD);    Brain-derived neurotrophic factor (BDNF);    Age at onset;    Genetic modifier;    Functional polymorphism;   

DOI  :  

来源: DOAJ

【 摘 要 】

In Huntington’s disease (HD), genetic factors in addition to the HD CAG repeat mutation play a significant role in determining age at neurologic onset. Brain-derived neurotrophic factor (BDNF), a survival factor for striatal neurons, has been implicated as a target of regulation by huntingtin and is an attractive candidate as a genetic modifier. We tested this hypothesis by genotyping a SNP known to alter BDNF function (rs6265, also termed Val66Met) and a SNP associated with Alzheimer disease (BDNF C270T), along with two BDNF intronic SNPs (rs7103411, rs11030104), in 228 cases with extreme young onset and 329 cases with extreme old onset of HD. No differences were seen between groups for allele frequencies or genotype frequencies for any SNP. Furthermore, no association to onset age was seen in GEE models controlling for HD repeat size or in haplotype analyses of these SNPs. These results indicate that BDNF does not influence significantly the mechanisms in HD pathogenesis that lead to neurologic onset.

【 授权许可】

Unknown