Aktuelle Neurologie 2005; 32 - P283
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

S Metzger 1, P Bauer 1, J Tomiuk 1, F Laccone 1, S DiDonato 1, C Gellera 1, H.W Lange 1, H Weirich-Schwaiger 1, B Melegh 1, V Havasi 1, L Baliko 1, J.T Epplen 1, J Zaremba 1, A Sulek 1, A.N Basak 1, E Soydan 1, J Zidovska 1, V Kebrdlova 1, M Pandolfo 1, P Ribai 1, L Kadasi 1, M Kvasnicova 1, B.H.F Weber 1, F Kreuz 1, M Dose 1, M Stuhrmann 1, O Riess 1
  • 1Tubingen, Göttingen; Milan, I; Dusseldorf; Innsbruck, A; Pecs, HUN; Bochum; Warsaw, PL; Istanbul, TR; Prague, CZ; Brussels, B; Bratislava, Bystrica, SVK; Wurzburg, Dresden, Taufkirchen, Hannover

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.