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DOI: 10.1055/s-2005-919317
Genetic analysis of candidate genes modifying the age-at-onset in Huntington's Disease: results of a large European association study
Huntington's disease (HD) is a neurodegenerative disorder, which is caused by an expansion of a polymorphic CAG repeat in the HD-gene encoding huntingtin. There is a strong inverse correlation between the number of expanded CAG repeats in HD patients and the median age-at-onset of HD. Statistical modelling attributes 42–73% of the variance to this single genetic factor. The remainder is determined by other genetic and environmental factors. To identify genetic modifiers of the age at disease onset, we identified a total of 15 polymorphisms in the GluR6, TBP, BDNF, HIP14, and HIP1 gene and analysed 6 of them by association studies in 875 independent European HD patients. An additional group of 156 affected sib pairs provided the opportunity to search for modifying effects on the age-at-onset in an independent HD sample. Although some of the factors have been defined as genetic modifier factors in previous studies, none of the examined polymorphisms showed a significant effect on the age-at-onset in the analyzed large sample of more than 1100 Caucasian HD patients.