Short report

PGC-1alpha as modifier of onset age in Huntington disease

Elahe Taherzadeh-Fard¹ , Carsten Saft² , Jürgen Andrich² , Stefan Wieczorek¹ and Larissa Arning¹

¹  Department of Human Genetics, Ruhr-University, 44780 Bochum, Germany

²  Department of Neurology, St. Josef-Hospital, Ruhr-University, 44791 Bochum, Germany

author email corresponding author email

Molecular Neurodegeneration 2009, 4:10doi:10.1186/1750-1326-4-10

Published:	6 February 2009

Abstract

Although there is a strong correlation between CAG repeat length and age at onset (AO) of motor symptoms, individual Huntington disease (HD) patients may differ dramatically in onset age and disease manifestations despite similar CAG repeat lengths. This has led to a search for genetic factors that influence AO. In order to identify such a genetic modifier, we analysed polymorphisms in the PGC-1alpha gene. Recent data indicate inhibition of PGC-1alpha function by mutant Htt supporting a link between transcriptional deregulation and mitochondrial dysfunction in HD. In > 400 HD patients, a polymorphism located within intron 2, a potential recombination hot spot, explains a small, but statistically significant, amount of the variability in AO. Our data suggest that PGC-1alpha has modifying effects on the pathogenic process in HD.