| 1. |
- Ahmadi, Ahmad, et al.
(författare)
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Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease
- 2012
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 522:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- Pesticide exposure has been suggested to increase the risk to develop Parkinson's disease (PD). The arylesterase paraoxonase 1 (PON1) is mainly expressed in the liver and hydrolyzes organophosphates such as pesticides. The polymorphism Leu54Met (rs854560) in PON1, impairing enzyme activity and leading to decreased PON1 expression levels, has been reported to be associated with Parkinson's disease (PD). PON1 is part of a cluster on chromosome 7q21.3 together with PON2 and PON3. We investigated the occurrence of four additional polymorphisms in PON1 and two in PON2 in a Swedish PD case-control material. We found a significant association (p = 0.007) with a PON1 promoter polymorphism, rs854571. The minor allele was more common among controls than PD cases which suggest a protective effect. This is strengthened by the fact that rs854571 is in strong linkage disequilibrium with another PON1 promoter polymorphism, rs854572, reported to increase PON1 gene expression. Our findings support the hypothesis that PON1 is involved in the etiology of PD and that higher PON1 levels are reducing the risk for PD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 2. |
- Ran, C., et al.
(författare)
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Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45
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Tidskriftsartikel (refereegranskat)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. (C) 2016 The Author(s). Published by Elsevier Inc.
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