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Background: The etiology of the most common form of dystonia, focal idiopathic torsion dystonia (F-ITD), remains poorly understood. There is growing evidence for a contributory role of inherited factors, but distinct genetic susceptibility factors have yet to be identified and reliably established. Mutations in the DYT1 gene can sometimes result in focal dystonia and an association with a polymorphism in the DR5 receptor gene (DRD5) has been reported, but awaits confirmation. Other factors previously implicated in the pathogenesis of F-ITD include autoimmune mechanisms and a disturbed homocysteine metabolism as well as a disturbed copper metabolism. Methods: We investigated a possible role of DYT1 polymorphisms and haplotypes, a CA repeat in the DR5 receptor gene (DRD5), the HLA-DRB locus, four polymorphisms in the homocysteine metabolism and copper genes (ATP7A and ATP7B) in the pathogenesis of F-ITD. Initially, 100 German patients and 100 matched controls were investigated. A second, French population with 120 F-ITD patients and matched controls was available to confirm or refute potentially interesting findings.
Results: Two polymorphisms of the beta-cystathionine synthase gene were associated with F-ITD in the German population. This finding could, however, not be replicated in a second, independent F-I-ITD patient and control group of French origin. None of the other investigated polymorphisms were associated with F-ITD. No changes in the investigated copper genes was found. In particular, we failed to confirm a previously reported association with a polymorphism in DRD5. Conclusion: Our data provide evidence against an involvement of copper genes, DYT1 haplotypes, DRD5, the HLA-DRB locus and polymorphisms in the homocysteine pathway in the pathogenesis of F-ITD. Further studies are needed to identify genetic susceptibility factors for F-ITD.