title: Synaptotagmin XI in Parkinson's disease: New evidence from an association study in Spain and Mexico.
abstract: BACKGROUND
  The pathophysiology of PD (Parkinson's disease) has been related to the ubiquitin proteasome system and oxidative stress. Parkin acts as ubiquitin ligase on several substrates. Because genetic variants often have different frequencies across populations, population specific analyses are necessary to complement and validate results from genome-wide association studies.
  
  
  METHODS
  We carried out an association study with genes coding for parkin substrates and cellular stress components in the Galician population (Northern Spain). SNCA and MAPT SNPs were also analyzed. We studied 75 SNPs in a discovery sample of 268 PD patients and 265 controls from Galicia. A replication sample of 271 patients and 260 controls was recruited from Mexico City.
  
  
  RESULTS
  We observed significant association between PD and SNPs in MAPT. Nominal p-values<0.05 were obtained in the Galician cohort for SNPs in SYT11, coding for synaptotagmin XI. These results were replicated in the Mexican sample.
  
  
  CONCLUSIONS
  The associated markers lie within a ~140kb strong linkage disequilibrium segment that harbors several candidate genes, including SYT11. SNPs from the GBA-SYT11-RAB25 region have been previously associated with PD, however the functionally relevant variants remain unknown. Our data support a likely role of genetic factors within 1q22 in PD susceptibility.
authors.affiliation: Department of Neurology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain. Electronic address: angel.sesar.ignacio@sergas.es.
authors.forename: Angel
authors.initials: A
authors.lastname: Sesar
authors.affiliation: Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Grupo de Medicina Xenómica, Fundación Pública Galega de Medicina Xenómica-SERGAS, Santiago de Compostela, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Cacheiro
authors.affiliation: Biological Systems Department, Universidad Autónoma Metropolitana, Campus Xochimilco, Mexico City, Mexico.
authors.forename: Marisol
authors.initials: M
authors.lastname: López-López
authors.affiliation: Grupo de Medicina Xenómica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Camiña-Tato
authors.affiliation: Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Grupo de Medicina Xenómica, Fundación Pública Galega de Medicina Xenómica-SERGAS, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institute of Health Carlos III, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Quintáns
authors.affiliation: Neurogenetics Department, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Mexico City, Mexico.
authors.forename: Nancy
authors.initials: N
authors.lastname: Monroy-Jaramillo
authors.affiliation: Neurogenetics Department, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Mexico City, Mexico.
authors.forename: María-Elisa
authors.initials: ME
authors.lastname: Alonso-Vilatela
authors.affiliation: Department of Neurology, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cebrián
authors.affiliation: Neurogenetics Department, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Mexico City, Mexico.
authors.forename: Petra
authors.initials: P
authors.lastname: Yescas-Gómez
authors.affiliation: Department of Neurology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Ares
authors.affiliation: Department of Neurology, Complejo Hospitalario Universitario de Coruña, La Coruña, Spain.
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: Rivas
authors.affiliation: Department of Neurology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Castro
authors.affiliation: Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Grupo de Medicina Xenómica, Fundación Pública Galega de Medicina Xenómica-SERGAS, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institute of Health Carlos III, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.affiliation: Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Grupo de Medicina Xenómica, Fundación Pública Galega de Medicina Xenómica-SERGAS, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institute of Health Carlos III, Spain.
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Sobrido
mesh_terms: D000368:Aged; D003431:Cross-Cultural Comparison; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D050857:Synaptotagmins / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: C054369:MAPT protein, human; C497604:SNCA protein, human; C494265:SYT11 protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; D050857:Synaptotagmins
keywords: 1q22; Association study; Parkinson's disease; SYT11; Single nucleotide polymorphism