Lack of evidence for an association between UCHL1 S18Y and Parkinson's disease

Authors: Hutter, Carolyn M.¹; Samii, Ali; Factor, Stewart A.²; Nutt, John G.³; Higgins, Donald S.⁴; Bird, Thomas D.; Griffith, Alida⁵; Roberts, John W.⁶; Leis, Berta C.⁵; Montimurro, Jennifer S.⁷; Kay, Denise M.⁷; Edwards, Karen L.¹; Payami, Haydeh⁷; Zabetian, Cyrus P.

Source: European Journal of Neurology, Volume 15, Number 2, February 2008 , pp. 134-139(6)

Publisher: Wiley-Blackwell

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Abstract:

UCHL1 has been proposed as a candidate gene for Parkinson's disease (PD). A meta-analysis of white and Asian subjects reported an inverse association between the non-synonymous UCHL1 S18Y polymorphism and PD risk. However, this finding was not replicated in a large case-control study and updated meta-analysis restricted to white subjects. We performed a case-control study of 1757 PD patients recruited from movement disorder clinics and 2016 unrelated controls from four regions of the United States. All subjects self-reported as white. We did not observe evidence for an association between S18Y genotypes and PD (overall P-value for association: P = 0.42). After adjustment for age, sex, and recruitment region, the odds ratio for Y/S versus S/S was 0.91 (95% CI: 0.78-1.06) and for Y/Y versus S/S was 0.87 (95% CI: 0.58-1.29). We also did not observe a significant association for recessive or dominant models of inheritance, or after stratification by age at onset, age at blood draw, sex, family history of PD, or recruitment region. Our results suggest that UCHL1 S18Y is not a major susceptibility factor for PD in white populations although we cannot exclude the possibility that the S18Y variant exerts weak effects on risk, particularly in early-onset disease.

Keywords: case-control study; neuroepidemiology; Parkinson's disease; UCHL1

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1468-1331.2007.02012.x

Affiliations: 1: Department of Epidemiology, University of Washington, Seattle, WA, USA 2: Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA 3: Department of Neurology, Oregon Health & Science University, Portland, OR, USA 4: Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, NY, USA 5: Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, WA, USA 6: Virginia Mason Medical Center, Seattle, WA, USA 7: Genomics Institute, Wadsworth Center, New York State Department of Health, Albany, NY, USA

Publication date: 2008-02-01

Lack of evidence for an association between UCHL1 S18Y and Parkinson's disease

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