STX6 rs1411478 is not associated with increased risk of Parkinson's disease.

A variant in Syntaxin 6 (a soluble N-ethylmaleimide-sensitive factor attachment protein receptor STX6) (rs1411478) has been shown to be associated with progressive supranuclear palsy (PSP). Although Parkinson's disease (PD) and PSP are distinct neurodegenerative diseases, they share some clinical and genetic features. In this study, we evaluated STX6 genetic variability in PD susceptibility in ethnically matched case-control series from Canada, Norway, Taiwan and Tunisia and we evaluated the presence of pathogenic mutations within families. No pathogenic mutations were found in STX6. Similarly, statistical analysis of rs1411478 failed to identify differences in genotype or allelic frequencies between cases and controls. Our results do not support a role for STX6 in PD.

[1]  Sonja W. Scholz,et al.  Genome-Wide Association Study reveals genetic risk underlying Parkinson’s disease , 2009, Nature Genetics.

[2]  I. Litvan.  Update on progressive supranuclear palsy , 2004, Current neurology and neuroscience reports.

[3]  Yusuke Nakamura,et al.  Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease , 2009, Nature Genetics.

[4]  S. Gilman,et al.  Diagnostic criteria for Parkinson disease. , 1999, Archives of neurology.

[5]  Reinhard Jahn,et al.  SNAREs — engines for membrane fusion , 2006, Nature Reviews Molecular Cell Biology.

[6]  Marc N. Offman,et al.  A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. , 2011, American journal of human genetics.

[7]  M. Farrer,et al.  Association of the MAPT locus with Parkinson’s disease , 2010, European journal of neurology.

[8]  C. Ide,et al.  Regulation of Growth Cone Extension by SNARE Proteins1 , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[9]  B. Tang,et al.  Syntaxin 12, a Member of the Syntaxin Family Localized to the Endosome* , 1998, The Journal of Biological Chemistry.

[10]  Bor Luen Tang,et al.  Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform , 2002, The Journal of cell biology.

[11]  Timothy Lynch,et al.  Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. , 2005, American journal of human genetics.

[12]  M. Farrer.  Genetics of Parkinson disease: paradigm shifts and future prospects , 2006, Nature Reviews Genetics.

[13]  N. Bright,et al.  Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5 , 2009, Journal of Cell Science.

[14]  K. Doheny,et al.  Genomewide association study for susceptibility genes contributing to familial Parkinson disease , 2009, Human Genetics.

[15]  M. Farrer,et al.  VPS35 mutations in Parkinson disease. , 2011, American journal of human genetics.

[16]  E. Tolosa,et al.  Different MAPT haplotypes are associated with Parkinson's disease and progressive supranuclear palsy , 2011, Neurobiology of Aging.

[17]  K. Kaestner,et al.  A Deleterious Mutation in DNAJC6 Encoding the Neuronal-Specific Clathrin-Uncoating Co-Chaperone Auxilin, Is Associated with Juvenile Parkinsonism , 2012, PloS one.

[18]  T. Südhof,et al.  α-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro , 2010, Science.

[19]  P. Cullen,et al.  Recent Advances in Retromer Biology , 2011, Traffic.

[20]  M. Tagaya,et al.  The Soluble N-Ethylmaleimide-Sensitive Factor Attached Protein Receptor Complex in Growth Cones: Molecular Aspects of the Axon Terminal Development , 1997, The Journal of Neuroscience.

[21]  Andrew J. Lees,et al.  Identification of common variants influencing risk of the tauopathy Progressive Supranuclear Palsy , 2011, Nature Genetics.

[22]  R. Scheller,et al.  Syntaxin-6 SNARE involvement in secretory and endocytic pathways of cultured pancreatic beta-cells. , 2004, Molecular biology of the cell.

[23]  J. Bonifacino,et al.  Canonical interaction of cyclin G associated kinase with adaptor protein 1 regulates lysosomal enzyme sorting. , 2007, Molecular biology of the cell.

[24]  J. Nutt,et al.  Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease , 2010, Nature Genetics.