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Genetic analysis of candidate genes modifying the age-at-onset in Huntington's disease.

par Metzger, Silke;Bauer, Peter;Tomiuk, Juergen;Laccone, Franco;Didonato, Stefano;Gellera, Cinzia;Mariotti, Christian;Lange, Herwig W;Weirich-Schwaiger, Helga;Wenning, Gregor K;Seppi, Klaus;Melegh, Bela;Havasi, Victoria;Balikó, Lazlo;Wieczorek, Stefan;Zaremba, Jacek;Hoffman-Zacharska, Dorota;Sulek, Anna;Basak, A Nazli;Soydan, Esra;Zidovska, Jana;Kebrdlova, Vera;Pandolfo, Massimo ;Ribaï, Pascale;Kadasi, Ludovit;Kvasnicova, Marta;Weber, Bernhard H F;Kreuz, Friedmar;Dose, Matthias;Stuhrmann, Manfred;Riess, Olaf
Référence Human genetics, 120, 2, page (285-292)
Publication Publié, 2006-09

Article révisé par les pairs

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Résumé :

The expansion of a polymorphic CAG repeat in the HD gene encoding huntingtin has been identified as the major cause of Huntington's disease (HD) and determines 42-73% of the variance in the age-at-onset of the disease. Polymorphisms in huntingtin interacting or associated genes are thought to modify the course of the disease. To identify genetic modifiers influencing the age at disease onset, we searched for polymorphic markers in the GRIK2, TBP, BDNF, HIP1 and ZDHHC17 genes and analysed seven of them by association studies in 980 independent European HD patients. Screening for unknown sequence variations we found besides several silent variations three polymorphisms in the ZDHHC17 gene. These and polymorphisms in the GRIK2, TBP and BDNF genes were analysed with respect to their association with the HD age-at-onset. Although some of the factors have been defined as genetic modifier factors in previous studies, none of the genes encoding GRIK2, TBP, BDNF and ZDHHC17 could be identified as a genetic modifier for HD.