title: Genetic analysis of candidate genes modifying the age-at-onset in Huntington's disease.
abstract: 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.
authors.affiliation: Department of Medical Genetics, University of Tübingen, Calwerstrasse 7, 72076, Tübingen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Metzger
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Tomiuk
authors.forename: Franco
authors.initials: F
authors.lastname: Laccone
authors.forename: Stefano
authors.initials: S
authors.lastname: Didonato
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
authors.forename: Herwig W
authors.initials: HW
authors.lastname: Lange
authors.forename: Helga
authors.initials: H
authors.lastname: Weirich-Schwaiger
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
authors.forename: Klaus
authors.initials: K
authors.lastname: Seppi
authors.forename: Bela
authors.initials: B
authors.lastname: Melegh
authors.forename: Viktoria
authors.initials: V
authors.lastname: Havasi
authors.forename: Laszlo
authors.initials: L
authors.lastname: Balikó
authors.forename: Stefan
authors.initials: S
authors.lastname: Wieczorek
authors.forename: Jacek
authors.initials: J
authors.lastname: Zaremba
authors.forename: Dorota
authors.initials: D
authors.lastname: Hoffman-Zacharska
authors.forename: Anna
authors.initials: A
authors.lastname: Sulek
authors.forename: A Nazli
authors.initials: AN
authors.lastname: Basak
authors.forename: Esra
authors.initials: E
authors.lastname: Soydan
authors.forename: Jana
authors.initials: J
authors.lastname: Zidovska
authors.forename: Vera
authors.initials: V
authors.lastname: Kebrdlova
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribaï
authors.forename: Ludovit
authors.initials: L
authors.lastname: Kadasi
authors.forename: Marta
authors.initials: M
authors.lastname: Kvasnicova
authors.forename: Bernhard H F
authors.initials: BH
authors.lastname: Weber
authors.forename: Friedmar
authors.initials: F
authors.lastname: Kreuz
authors.forename: Matthias
authors.initials: M
authors.lastname: Dose
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic; D018092:Kainic Acid Receptors / Q000235:genetics; D035181:TATA-Box Binding Protein / Q000235:genetics / Q000378:metabolism; D000097806:GluK2 Kainate Receptor
chemical_list: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D018092:Kainic Acid Receptors; D035181:TATA-Box Binding Protein; D000097806:GluK2 Kainate Receptor; C073368:HIP1 protein, human; C086055:HTT protein, human; C473038:ZDHHC17 protein, human