Angel Sesar1, Pilar Cacheiro2, Marisol López-López3, Montserrat Camiña-Tato4, Beatriz Quintáns5, Nancy Monroy-Jaramillo6, María-Elisa Alonso-Vilatela6, Ernesto Cebrián7, Petra Yescas-Gómez6, Begoña Ares8, María-Teresa Rivas9, Alfonso Castro8, Angel Carracedo5, María-Jesús Sobrido5. 1. 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. 2. 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. 3. Biological Systems Department, Universidad Autónoma Metropolitana, Campus Xochimilco, Mexico City, Mexico. 4. Grupo de Medicina Xenómica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain. 5. 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. 6. Neurogenetics Department, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Mexico City, Mexico. 7. Department of Neurology, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain. 8. 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. 9. Department of Neurology, Complejo Hospitalario Universitario de Coruña, La Coruña, Spain.
Abstract
INTRODUCTION: 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. DISCUSSION: 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.
INTRODUCTION: 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 PDpatients 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. DISCUSSION: 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.