Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 274-279 |
| Number of pages | 6 |
| Journal | Neurobiology of Disease |
| Volume | 24 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Nov 2006 |
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Keywords
- Age-at-onset
- BDNF
- Genetic modifiers
- Huntington's disease
- Regression analysis
- Val66Met polymorphism
ASJC Scopus subject areas
- Neurology
Cite this
No evidence of association between BDNF gene variants and age-at-onset of Huntington's disease. / Di Maria, Emilio; Marasco, Antonella; Tartari, Marzia; Ciotti, Paola; Abbruzzese, Giovanni; Novelli, Giuseppe; Bellone, Emilia; Cattaneo, Elena; Mandich, Paola.
In: Neurobiology of Disease, Vol. 24, No. 2, 11.2006, p. 274-279.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - No evidence of association between BDNF gene variants and age-at-onset of Huntington's disease
AU - Di Maria, Emilio
AU - Marasco, Antonella
AU - Tartari, Marzia
AU - Ciotti, Paola
AU - Abbruzzese, Giovanni
AU - Novelli, Giuseppe
AU - Bellone, Emilia
AU - Cattaneo, Elena
AU - Mandich, Paola
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
KW - Age-at-onset
KW - BDNF
KW - Genetic modifiers
KW - Huntington's disease
KW - Regression analysis
KW - Val66Met polymorphism
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UR - http://www.scopus.com/inward/citedby.url?scp=33750209146&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2006.07.002
DO - 10.1016/j.nbd.2006.07.002
M3 - Article
C2 - 16905325
AN - SCOPUS:33750209146
VL - 24
SP - 274
EP - 279
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 2
ER -