Volume 33, Issue 4 p. 637-641
Brief Report

α-synuclein (SNCA) but not dynamin 3 (DNM3) influences age at onset of leucine-rich repeat kinase 2 (LRRK2) Parkinson's disease in Spain

Rubén Fernández-Santiago PhD

Corresponding Author

Rubén Fernández-Santiago PhD

Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Clinical and Experimental Research, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Corresponding authors: Drs. R. Fernández-Santiago and M. Ezquerra, Laboratory of Neurodegenerative Diseases, CELLEX building, Faculty of Medicine (UB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, University of Barcelona, Casanova 143, Floor 3B, 08036, Barcelona; E-mail: [email protected]; E-mail: [email protected]Search for more papers by this author
Alicia Garrido MD

Alicia Garrido MD

Movement Disorders Unit, Department of Neurology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

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Jon Infante MD, PhD

Jon Infante MD, PhD

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Movement Disorders Unit, Department of Neurology, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain

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Isabel González-Aramburu MD

Isabel González-Aramburu MD

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Movement Disorders Unit, Department of Neurology, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain

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María Sierra MD, PhD

María Sierra MD, PhD

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Movement Disorders Unit, Department of Neurology, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain

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Manel Fernández

Manel Fernández

Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Clinical and Experimental Research, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

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Francesc Valldeoriola MD, PhD

Francesc Valldeoriola MD, PhD

Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Clinical and Experimental Research, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Movement Disorders Unit, Department of Neurology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

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Esteban Muñoz MD, PhD

Esteban Muñoz MD, PhD

Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Clinical and Experimental Research, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Movement Disorders Unit, Department of Neurology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

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Yaroslau Compta MD, PhD

Yaroslau Compta MD, PhD

Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Clinical and Experimental Research, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Movement Disorders Unit, Department of Neurology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

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María-José Martí MD, PhD

María-José Martí MD, PhD

Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Clinical and Experimental Research, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Movement Disorders Unit, Department of Neurology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

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José Ríos MSc

José Ríos MSc

Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer and Hospital Clinic, Barcelona, Spain

Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain

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Eduardo Tolosa MD, PhD

Eduardo Tolosa MD, PhD

Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Clinical and Experimental Research, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Movement Disorders Unit, Department of Neurology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

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Mario Ezquerra PhD

Corresponding Author

Mario Ezquerra PhD

Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, Clinical and Experimental Research, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain

Corresponding authors: Drs. R. Fernández-Santiago and M. Ezquerra, Laboratory of Neurodegenerative Diseases, CELLEX building, Faculty of Medicine (UB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, University of Barcelona, Casanova 143, Floor 3B, 08036, Barcelona; E-mail: [email protected]; E-mail: [email protected]Search for more papers by this author
the Barcelona LRRK2 Study Group†

the Barcelona LRRK2 Study Group†

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First published: 23 February 2018
Citations: 22

See appendix.

Rubén Fernández-Santiago and Alicia Garrido contributed equally to this work. Eduardo Tolosa and Mario Ezquerra are cosenior authors. Members of the Barcelona LRRK2 Study Group are listed in the Acknowledgments.

Funding agencies: This work was supported by the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas to the Movement Disorders Unit of the Neurology Service from the Hospital Clínic de Barcelona to E.T., M.-J.M., R.F.-S., M.E., F.V., E.M., and Y.C. (Grant PRI-16-2017). R.F.-S. was supported by a Jóvenes Investigadores grant of the Spanish Ministry of Economy and Competitiveness (Grant SAF2015-73508-JIN, Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional/Unión Europea (AEI/FEDER/UE)), and M.E. by a Miguel Servet contract of the Instituto de Salud Carlos III (ISCIII)/Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).

Relevant conflicts of interests/financial disclosures: Nothing to report.

ABSTRACT

Objectives: A recent study showed that Arab-Berbers GG homozygous at rs2421947(C/G) in the dynamin 3 gene (DNM3) had 12.5 years earlier age at onset of leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD) (L2PD). We explored whether this variant modulates the L2PD age at onset in Spain.

Methods: We genotyped rs2421947 in 329 participants (210 L2PD patients, 119 L2PD nonmanifesting p.G2019S carriers), and marker rs356219 (A/G) in the α-synuclein gene (SNCA).

Results: By Kaplan Meier and Cox regression analyses, we did not find an association of the DNM3 polymorphism with L2PD age at onset. However, we found an association of the SNCA marker with up to an 11 years difference in the L2PD median age at onset (58 years for GG carriers vs 69 years for AA).

Conclusion: Our results indicate that SNCA rs356219 but not dynamin 3 DNM3 rs2421947 modifies the penetrance of the mutation G2019S in the Spanish population by influencing the L2PD age at onset. These findings suggest that different genetic modifiers may influence the L2PD age at onset in different populations. © 2018 International Parkinson and Movement Disorder Society