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. 2016 Sep:45:212.e5-212.e11.
doi: 10.1016/j.neurobiolaging.2016.04.022. Epub 2016 May 3.

Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden

Caroline Ran  1 , Lovisa Brodin  2 , Lars Forsgren  3 , Marie Westerlund  4 , Mehrafarin Ramezani  1 , Sandra Gellhaar  1 , Fengqing Xiang  5 , Camilla Fardell  6 , Hans Nissbrandt  6 , Peter Söderkvist  7 , Andreas Puschmann  8 , Emil Ygland  9 , Lars Olson  1 , Thomas Willows  2 , Anders Johansson  2 , Olof Sydow  2 , Karin Wirdefeldt  10 , Dagmar Galter  1 , Per Svenningsson  2 , Andrea Carmine Belin  11
Affiliations

Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden

Caroline Ran et al. Neurobiol Aging. 2016 Sep.

Abstract

Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology.

Keywords: GBA; Gaucher's disease; Genetics; Lysosome; α-Synuclein.

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