No evidence of association between BDNF gene variants and age-at-onset of Huntington's disease.
Huntington's disease (HD) is a late-onset, autosomal dominant neurodegenerative disease caused by a CAG trinucleotide expansion. The number of repeats on the HD chromosome explains most of the variability in age of onset, but genetic factors other than the HD gene are responsible for part of the residual variance. Based on the role played by the brain derived neurotrophic factor (BDNF) in neurodysfunction and neurodegeneration in HD, we searched for novel polymorphisms in the neuron restrictive silencer element located in the BDNF promoter. Then, the effect of the Val66Met variant in determining age of onset was tested in a large sample of HD carriers by using a multivariate regression approach. The CAG repeat number accounted for 62% of the variance. After correction for the predominant effect of the CAG expansion, no multiple regression model provided evidence of association between the Val66Met genotype and variation in age-at-onset. Additional studies are warranted to further investigate BDNF as genetic modifier of the HD phenotype.
Di Maria
Emilio
E
Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, and Medical Genetics Unit, San Martino Hospital, Genova, Italy. emilio.dimaria@unige.it
Marasco
Antonella
A
Tartari
Marzia
M
Ciotti
Paola
P
Abbruzzese
Giovanni
G
Novelli
Giuseppe
G
Bellone
Emilia
E
Cattaneo
Elena
E
Mandich
Paola
P
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D037941:Silencer Elements, Transcriptional / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D014633:Valine / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine