Background Huntington disease (HD) is caused by an autosomal dominant CAG repeat expansion in the htt gene. HD symptoms include neurologic, psychiatric and cognitive and metabolic abnormalities. In addition to the CAG repeat mutation other genetic factors termed disease modifiers determine symptom onset and disease progression. Some evidence suggests that the metabolic master regulator is such a modifier. We showed that the PPARGCA1A gene locus is larger than previously thought.
Aims We sought to determine whether SNPs in the expanded PPARGC1A gene locus modify age of onset in HD patients.
Results We report that a novel SNP located in the expanded PPARGC1A gene locus is associated with a delayed age of onset of motor symptoms in a large European HD cohort (REGISTRY cohort).
Conclusions This finding provides further support for a role of the PGC-1A signalling axis in the pathogenesis of HD and as a potential therapeutic target.
- genetic modifier
- metabolic dysregulation