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

Movement Disorders : Official Journal of the Movement Disorder Society
Rubén Fernández-SantiagoBarcelona LRRK2 Study Group†

Abstract

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. 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). 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). 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.

References

Mar 1, 1992·Journal of Neurology, Neurosurgery, and Psychiatry·A J HughesA J Lees
Aug 3, 2007·The New England Journal of Medicine·Travis DunckleyDietrich A Stephan
Sep 11, 2007·Lancet Neurology·Michael A van EsLeonard H van den Berg
Dec 29, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Julia FuchsThomas Gasser
Jun 10, 2008·Lancet Neurology·Daniel G HealyUNKNOWN International LRRK2 Consortium
May 26, 2009·Neurobiology of Aging·Rubén Fernández-SantiagoThomas Gasser
Nov 17, 2009·Lancet Neurology·Dennis W DicksonIrene Litvan
Nov 10, 2010·Archives of Neurology·Ignacio F MataCyrus P Zabetian
Jun 30, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Stefano GoldwurmGianni Pezzoli
Sep 29, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·María SierraJon Infante
Jun 7, 2012·Journal of Molecular Neuroscience : MN·Teresa Botta-OrfilaEduard Tolosa
May 16, 2013·Movement Disorders : Official Journal of the Movement Disorder Society·Kathrin BrockmannThomas Gasser
Oct 11, 2014·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J TrinhM J Farrer
Oct 21, 2014·JAMA Neurology·Joanne TrinhMatthew James Farrer
Jun 13, 2015·Neurology·Karen MarderUNKNOWN LRRK2 Ashkenazi Jewish Consortium
Apr 20, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Connie MarrasUNKNOWN LRRK2 Cohort Consortium

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Citations

Aug 23, 2018·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J N FooE-K Tan
Jun 25, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Rubén Fernández-SantiagoCristina Malagelada
Jan 21, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Hirotaka IwakiAndrew B Singleton
Jul 25, 2019·Clinical Epigenetics·Rubén Fernández-SantiagoMario Ezquerra
Sep 26, 2019·Frontiers in Human Neuroscience·Chao RenPeiyuan Yin
Jan 9, 2019·Frontiers in Neuroanatomy·Natalia López-González Del ReyJavier Blesa
Jun 19, 2019·Cell Death and Differentiation·Tony ValenteJosep Saura
Sep 26, 2020·Bioscience Reports·Evy LobbestaelVeerle Baekelandt
Jan 27, 2021·International Journal of Molecular Sciences·Vinita G Chittoor-VinodBirgitt Schüle
May 4, 2021·Annals of Neurology·Dongbing LaiTatiana Foroud

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