Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington's disease.
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.
Kishikawa
Shotaro
S
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, and Department of Neurology, Boston University School of Medicine, MA 02114, USA.
Li
Jian-Liang
JL
Gillis
Tammy
T
Hakky
Michael M
MM
Warby
Simon
S
Hayden
Michael
M
MacDonald
Marcy E
ME
Myers
Richard H
RH
Gusella
James F
JF
D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006816:Huntington Disease / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D007438:Introns / Q000235:genetics; D008715:Methionine / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D014633:Valine / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine