Common polymorphisms in dystonia-linked genes and susceptibility to the sporadic primary dystonias

Parkinsonism Relat Disord. 2012 May;18(4):351-7. doi: 10.1016/j.parkreldis.2011.11.024. Epub 2011 Dec 14.


Genes involved in familial dystonia syndromes (DYT genes) are ideal candidates for investigating whether common genetic variants influence the susceptibility to sporadic primary dystonia. To date, there have been few candidate gene studies for primary dystonia and only two DYT genes, TOR1A and THAP1, have been assessed. We therefore employed a haplotype-tagging strategy to comprehensively assess if common polymorphisms in eight DYT genes (TOR1A, TAF1, GCH1, THAP1, MR-1 (PNKD), SGCE, ATP1A3 and PRKRA) confer risk for sporadic primary dystonia. The 230 primary dystonia cases were matched for age and gender to 228 controls, recruited from movement disorder clinics in Brisbane, Australia and the Australian electoral roll. All subjects were genotyped for 56 tagging SNPs and genotype associations were investigated. Modest genotypic associations (P<0.05) were observed for three GCH1 SNPs (rs12147422, rs3759664 and rs10483639) when comparing all cases against controls. Associations were also seen when the cases were stratified based on presentation. Overall, our findings do not support the hypothesis that common TOR1A variants affect susceptibility for sporadic primary dystonia, and that it is unlikely that common variants around the DYT genes confer substantial risk for sporadic primary dystonia. Further work is warranted to follow up the GCH1 SNPs and the subgroup analyses.

MeSH terms

  • Aged
  • Australia
  • Case-Control Studies
  • Dystonic Disorders / genetics*
  • Female
  • GTP Cyclohydrolase / genetics*
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Molecular Chaperones / genetics*
  • Polymorphism, Single Nucleotide*


  • Molecular Chaperones
  • TOR1A protein, human
  • GTP Cyclohydrolase