Camilla J Kobylecki1, Børge G Nordestgaard1,2, Shoaib Afzal1. 1. Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. 2. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Herlev, Denmark.
Abstract
OBJECTIVE: Urate is a potent antioxidant, and high plasma urate has been associated with lower incidence of Parkinson's disease (PD) in epidemiological studies. We tested the hypothesis that high concentrations of plasma urate are associated with low incidence of PD. METHODS: We performed observational and genetic analyses using plasma urate and the urate SLC2A9 rs7442295 and ABCG2 rs2231142 genotype in >102,000 individuals from the CGPS (Copenhagen General Population Study). Information on PD and mortality was from national patient and death registries. Incidences of PD were calculated using Cox regression, Fine and Gray competing-risks regression, and instrumental variable analyses. RESULTS: In total, 398 individuals were diagnosed with PD, of which 285 were incident cases. The multivariable adjusted hazard ratio for PD was 0.56 (95% confidence interval [CI], 0.41-0.77) for the highest versus the lowest tertile of plasma urate (p for trend across 3 groups, 8 × 10-5 ). Each one-allele increase in the combined allele score was associated with 19μmol/l (95% CI, 18.5-19.9) higher plasma urate. In observational analyses, a 50μmol/l higher plasma urate was associated with a hazard ratio of 0.85 (0.77-0.92) for PD; in instrumental variable analyses, 50μmol/l higher plasma urate was associated with an odds ratio of 1.20 (0.85-1.71) for PD. INTERPRETATION: High plasma urate was associated with lower risk of PD in observational analyses; however, in instrumental variable analysis, high plasma urate was not associated with low risk of PD. Thus, our data do not support a causal relationship between high plasma urate and low risk of PD. Ann Neurol 2018;84:178-190.
OBJECTIVE:Urate is a potent antioxidant, and high plasma urate has been associated with lower incidence of Parkinson's disease (PD) in epidemiological studies. We tested the hypothesis that high concentrations of plasma urate are associated with low incidence of PD. METHODS: We performed observational and genetic analyses using plasma urate and the urateSLC2A9rs7442295 and ABCG2rs2231142 genotype in >102,000 individuals from the CGPS (Copenhagen General Population Study). Information on PD and mortality was from national patient and death registries. Incidences of PD were calculated using Cox regression, Fine and Gray competing-risks regression, and instrumental variable analyses. RESULTS: In total, 398 individuals were diagnosed with PD, of which 285 were incident cases. The multivariable adjusted hazard ratio for PD was 0.56 (95% confidence interval [CI], 0.41-0.77) for the highest versus the lowest tertile of plasma urate (p for trend across 3 groups, 8 × 10-5 ). Each one-allele increase in the combined allele score was associated with 19μmol/l (95% CI, 18.5-19.9) higher plasma urate. In observational analyses, a 50μmol/l higher plasma urate was associated with a hazard ratio of 0.85 (0.77-0.92) for PD; in instrumental variable analyses, 50μmol/l higher plasma urate was associated with an odds ratio of 1.20 (0.85-1.71) for PD. INTERPRETATION: High plasma urate was associated with lower risk of PD in observational analyses; however, in instrumental variable analysis, high plasma urate was not associated with low risk of PD. Thus, our data do not support a causal relationship between high plasma urate and low risk of PD. Ann Neurol 2018;84:178-190.
Authors: Michael A Schwarzschild; Alberto Ascherio; Cindy Casaceli; Gary C Curhan; Rebecca Fitzgerald; Cornelia Kamp; Codrin Lungu; Eric A Macklin; Kenneth Marek; Dariush Mozaffarian; David Oakes; Alice Rudolph; Ira Shoulson; Aleksandar Videnovic; Burton Scott; Lisa Gauger; Jason Aldred; Melissa Bixby; Jill Ciccarello; Steven A Gunzler; Claire Henchcliffe; Matthew Brodsky; Kellie Keith; Robert A Hauser; Christopher Goetz; Mark S LeDoux; Vanessa Hinson; Rajeev Kumar; Alberto J Espay; Joohi Jimenez-Shahed; Christine Hunter; Chadwick Christine; Aaron Daley; Maureen Leehey; J Antonelle de Marcaida; Joseph Harold Friedman; Albert Hung; Grace Bwala; Irene Litvan; David K Simon; Tanya Simuni; Cynthia Poon; Mya C Schiess; Kelvin Chou; Ariane Park; Danish Bhatti; Carolyn Peterson; Susan R Criswell; Liana Rosenthal; Jennifer Durphy; Holly A Shill; Shyamal H Mehta; Anwar Ahmed; Andres F Deik; John Y Fang; Natividad Stover; Lin Zhang; Richard B Dewey; Ashley Gerald; James T Boyd; Emily Houston; Valerie Suski; Sherri Mosovsky; Leslie Cloud; Binit B Shah; Marie Saint-Hilaire; Raymond James; Sarah Elizabeth Zauber; Stephen Reich; David Shprecher; Rajesh Pahwa; April Langhammer; Kathrin LaFaver; Peter A LeWitt; Patricia Kaminski; John Goudreau; Doozie Russell; David J Houghton; Ashley Laroche; Karen Thomas; Martha McGraw; Zoltan Mari; Carmen Serrano; Karen Blindauer; Marcie Rabin; Roger Kurlan; John C Morgan; Michael Soileau; Melissa Ainslie; Ivan Bodis-Wollner; Ruth B Schneider; Cheryl Waters; Amber Servi Ratel; Christopher A Beck; Patrick Bolger; Katherine F Callahan; Grace F Crotty; David Klements; Melissa Kostrzebski; Gearoid Michael McMahon; Lindsay Pothier; Sushrut S Waikar; Anthony Lang; Tiago Mestre Journal: JAMA Date: 2021-09-14 Impact factor: 56.272