title: Cervical dystonia and genetic common variation in the dopamine pathway.
abstract: Cervical dystonia, a late onset focal dystonia, has a complex genetic background. Multiple lines of evidence point to a role for aberrant dopamine levels in dystonia. We assessed whether common variation within genes that regulate brain dopamine levels and in key genes of the dopamine metabolic pathway, modulate the risk for cervical dystonia. DNA was collected from 363 Dutch CD patients and a cohort of Dutch control individuals. Haplotype-tagging single nucleotide polymorphisms (SNPs) complemented with selected variants of functional importance in COMT, DAT, TH, MAO-A and -B, DDC and DBH were investigated. We tested the 143 markers in single-SNP, haplotype and epistasis analyses. We did not find an association with any of the selected 143 SNPs in these key dopamine genes. Our data shows that common variations in key genes of the dopamine pathway do not contribute to dystonia risk in the Dutch population. Possibly, risk alleles in this pathway may be rarer than detectable in this study, or might be located in downstream dopamine signaling pathway. Alternatively, found dopamine level changes are secondary to the dystonia disease processes.
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. justus.groen@gmail.com
authors.forename: Justus L
authors.initials: JL
authors.lastname: Groen
authors.forename: Javier
authors.initials: J
authors.lastname: Simón-Sánchez
authors.forename: Katja
authors.initials: K
authors.lastname: Ritz
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Bochdanovits
authors.forename: Yue
authors.initials: Y
authors.lastname: Fang
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: van Hilten
authors.forename: Majid
authors.initials: M
authors.lastname: Aramideh
authors.forename: Bart P
authors.initials: BP
authors.lastname: van de Warrenburg
authors.forename: Agnita J W
authors.initials: AJ
authors.lastname: Boon
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.forename: Marina A J
authors.initials: MA
authors.lastname: Tijssen
mesh_terms: D004298:Dopamine / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D014103:Torticollis / Q000235:genetics*
chemical_list: D004298:Dopamine