The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited.

Journal: Movement disorders : official journal of the Movement Disorder Society

Volume: 37

Issue: 9

Year of Publication: 2022

Affiliated Institutions:  Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Team "Exposome, Heredity, Cancer, and Health", CESP, Villejuif, France. Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, Nantes, France. Centre for Genetic Epidemiology, Institute for Clinical Epidemiology, and Applied Biometry, University of Tubingen, Tübingen, Germany. Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, Tübingen, Germany. Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg. Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany. Molecular Genetics Section, Laboratory of Neurogenetics, NIA, NIH, Bethesda, Maryland, USA. Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia. Department of Neurology, Medical University of Vienna, Wien, Austria. Department of Neurology, Klinik Ottakring, Vienna, Austria. Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada. Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Australia. Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia. Department of Neurologie, Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France. Univ. Lille, Inserm, CHU Lille, UMR-S - LilNCog- Centre de Recherche Lille Neurosciences and Cognition, Lille, France. Department of Neurology, Ludwig Maximilians University of Munich, Munich, Germany. Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece. st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Department of Molecular Medicine, University of Pavia, Pavia, Italy. UOC Medical Genetics and Advanced Cell Diagnostics, S. Andrea University Hospital, Rome, Italy. Department of Biomedical Sciences, Humanitas University, Milan, Italy. Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini/CTO, Milan, Italy. Parkinson Institute, Fontazione Grigioni, Milan, Italy. Department of Neurology, San Gerardo Hospital, Monza, Italy. Institute for Biomedical Research and Innovation, National Research Council, Cosenza, Italy. Institute of Neurology, Magna Graecia University, Catanzaro, Italy. Institute of Molecular Bioimaging and Physiology National Research Council, Catanzaro, Italy. Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan. Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea. Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg. Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands. Department of Neurology, St Olav's Hospital and Norwegian University of Science and Technology, Trondheim, Norway. Department of Neurology, Oslo University Hospital, Oslo, Norway. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa. Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. Lab of Parkinson Disease and Other Neurodegenerative Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Institut de Neurociències, Universitat de Barcelona, Barcelona, Catalonia, Spain. Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Barcelona, Spain. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Department of Clinical Sciences Lund, Neurology, Lund University, Skåne University Hospital, Lund, Sweden. University of Birmingham and Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom. Faculty of Medicine, Health and Life Sciences, Queens University, Belfast, United Kingdom. Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.

Abstract summary 

Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions.To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction.We genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA-DRB1.At the amino acid level, a valine at position 11 (V11) in HLA-DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59-0.93, P  = 0.028). In silico predictions of the influence of V11 and smoking-induced modifications of α-synuclein on binding affinity showed findings consistent with this interaction pattern.Despite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Authors & Co-authors:  Domenighetti Cloé C Douillard Venceslas V Sugier Pierre-Emmanuel PE Sreelatha Ashwin Ashok Kumar AAK Schulte Claudia C Grover Sandeep S May Patrick P Bobbili Dheeraj R DR Radivojkov-Blagojevic Milena M Lichtner Peter P Singleton Andrew B AB Hernandez Dena G DG Edsall Connor C Gourraud Pierre-Antoine PA Mellick George D GD Zimprich Alexander A Pirker Walter W Rogaeva Ekaterina E Lang Anthony E AE Koks Sulev S Taba Pille P Lesage Suzanne S Brice Alexis A Corvol Jean-Christophe JC Chartier-Harlin Marie-Christine MC Mutez Eugénie E Brockmann Kathrin K Deutschländer Angela B AB Hadjigeorgiou Georges M GM Dardiotis Efthimos E Stefanis Leonidas L Simitsi Athina Maria AM Valente Enza Maria EM Petrucci Simona S Duga Stefano S Straniero Letizia L Zecchinelli Anna A Pezzoli Gianni G Brighina Laura L Ferrarese Carlo C Annesi Grazia G Quattrone Andrea A Gagliardi Monica M Matsuo Hirotaka H Nakayama Akiyoshi A Hattori Nobutaka N Nishioka Kenya K Chung Sun Ju SJ Kim Yun Joong YJ Kolber Pierre P van de Warrenburg Bart P C BPC Bloem Bastiaan R BR Aasly Jan J Toft Mathias M Pihlstrøm Lasse L Correia Guedes Leonor L Ferreira Joaquim J JJ Bardien Soraya S Carr Jonathan J Tolosa Eduardo E Ezquerra Mario M Pastor Pau P Diez-Fairen Monica M Wirdefeldt Karin K Pedersen Nancy L NL Ran Caroline C Belin Andrea C AC Puschmann Andreas A Ygland Rödström Emil E Clarke Carl E CE Morrison Karen E KE Tan Manuela M Krainc Dimitri D Burbulla Lena F LF Farrer Matt J MJ Krüger Rejko R Gasser Thomas T Sharma Manu M Vince Nicolas N Elbaz Alexis A

Study Outcome 

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Statistics
Citations :  Hollenbach JA, Norman PJ, Creary LE, et al. A specific amino acid motif of HLA-DRB1 mediates risk and interacts with smoking history in Parkinson’s disease. Proc Natl Acad Sci U S A 2019;116:7419–7424.
Authors :  81
Identifiers
Doi : 10.1002/mds.29133
SSN : 1531-8257
Study Population
Male,Female
Mesh Terms
Genetic Predisposition to Disease
Other Terms
HLA;Parkinson's disease;gene-environment interaction;smoking
Study Design
Cross Sectional Study
Study Approach
Country of Study
Publication Country
United States