TY - JOUR
T1 - Cervical dystonia and genetic common variation in the dopamine pathway
AU - Groen, J.L.
AU - Simon Sanchez, J.
AU - Ritz, K.
AU - Bochdanovits, Z.
AU - Fang, Y.
AU - van Hilten, J.J.
AU - Aramideh, M.
AU - van de Warrenburg, B.P.
AU - Boon, A.J.
AU - Baas, F.
AU - Heutink, P.
AU - Tijssen, M.A.
PY - 2013
Y1 - 2013
N2 - 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. © 2012.
AB - 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. © 2012.
U2 - https://doi.org/10.1016/j.parkreldis.2012.08.016
DO - https://doi.org/10.1016/j.parkreldis.2012.08.016
M3 - Article
C2 - 22981186
SN - 1353-8020
VL - 19
SP - 346
EP - 349
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 3
ER -
