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

Silke Metzger; Peter Bauer; Jürgen Tomiuk; Franco Laccone; Stefano Didonato; Cinzia Gellera; Caterina Mariotti; Herwig W Lange; Helga Weirich-Schwaiger; Gregor K Wenning; Klaus Seppi; Bela Melegh; Viktoria Havasi; Laszlo Balikó; Stefan Wieczorek; Jacek Zaremba; Dorota Hoffman-Zacharska; Anna Sulek; A Nazli Basak; Esra Soydan; Jana Zidovska; Vera Kebrdlova; Massimo Pandolfo; Pascale Ribaï; Ludovit Kadasi; Marta Kvasnicova; Bernhard H F Weber; Friedmar Kreuz; Matthias Dose; Manfred Stuhrmann; Olaf Riess

doi:10.1007/s00439-006-0221-2

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

Hum Genet. 2006 Sep;120(2):285-92. doi: 10.1007/s00439-006-0221-2. Epub 2006 Jul 18.

Affiliation

¹ Department of Medical Genetics, University of Tübingen, Calwerstrasse 7, 72076, Tübingen, Germany.

PMID: 16847693
DOI: 10.1007/s00439-006-0221-2

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acyltransferases
Adaptor Proteins, Signal Transducing
Adolescent
Adult
Age of Onset
Aged
Aged, 80 and over
Brain-Derived Neurotrophic Factor / genetics
Brain-Derived Neurotrophic Factor / metabolism
Carrier Proteins / genetics
Carrier Proteins / metabolism
Child
Child, Preschool
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
GluK2 Kainate Receptor
Humans
Huntingtin Protein
Huntington Disease / epidemiology*
Huntington Disease / genetics*
Huntington Disease / metabolism
Middle Aged
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Nuclear Proteins / metabolism
Polymorphism, Genetic*
Receptors, Kainic Acid / genetics
TATA-Box Binding Protein / genetics
TATA-Box Binding Protein / metabolism

Substances

Adaptor Proteins, Signal Transducing
Brain-Derived Neurotrophic Factor
Carrier Proteins
DNA-Binding Proteins
HIP1 protein, human
HTT protein, human
Huntingtin Protein
Nerve Tissue Proteins
Nuclear Proteins
Receptors, Kainic Acid
TATA-Box Binding Protein
Acyltransferases
ZDHHC17 protein, human