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Parkinsonism Relat Disord. 2018 Aug;53:4-9. doi: 10.1016/j.parkreldis.2018.04.031. Epub 2018 May 1.

Genetic variants related to urate and risk of Parkinson's disease.

Author information

1
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: kch460@mail.harvard.edu.
2
Department of Nutritional Health, The Pennsylvania State University, University Park, PA, USA.
3
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; School of Public Health, College of Medicine, University College Cork, Ireland.
4
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
5
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
6
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
7
MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston, MA, USA.
8
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Abstract

INTRODUCTION:

Higher urate concentrations have been associated with a lower risk of developing Parkinson's disease (PD) and with slower rates of clinical decline in PD patients. Whether these associations reflect a neuroprotective effect of urate is unclear. Our objective was to assess whether genetic variants that modify circulating urate levels are also associated with altered PD risk.

METHODS:

Participants were from three large ongoing cohort studies: the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Cancer Prevention Study II Nutrition Cohort (CPS-IIN). We examined associations between single nucleotide polymorphisms (SNPs) in SLC2A9 and other genes involved in urate transport and PD risk using conditional logistic regression among 1451 cases and 3135 matched controls. We assessed associations between SNPs and plasma urate levels in a subset of 1174 control participants with linear regression models.

RESULTS:

We found the expected associations between SNPs in SLC2A9 and plasma urate levels among men and women; however, SNPs in other genes tended not to be associated with urate. Each SNP in SLC2A9 explained less than 7% of the variance in plasma urate. We did not find significant associations between the SNPs in SLC2A9 and PD risk among men or women.

CONCLUSION:

Our results do not support an association between genetic variants associated with circulating urate levels and risk of PD, but larger investigations are needed to determine whether the modest genetic effects on blood urate contribute to predict PD risk.

KEYWORDS:

Parkinson's disease; Urate

Comment in

PMID:
29789205
PMCID:
PMC6120767
DOI:
10.1016/j.parkreldis.2018.04.031
[Indexed for MEDLINE]
Free PMC Article

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