Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease |
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Authors: | Andrea Carmine Belin Caroline Ran Anna Anvret Silvia Paddock Marie Westerlund Anna Håkansson Hans Nissbrandt Peter Söderkvist Nil Dizdar Ahmad Ahmadi Maria Anvret Thomas Willows Olof Sydow Dagmar Galter |
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Institution: | 1. Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden;2. Department of Pharmacology, Sahlgrenska Academy at Göteborg University, 40530 Göteborg, Sweden;3. Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 58185 Linköping, Sweden;4. Department of Neurology, University Hospital, Linköping University, 58185 Linköping, Sweden;5. Department of Neurology, Karolinska University Hospital, 17176 Stockholm, Sweden |
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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. |
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Keywords: | Pesticide Linkage disequilibrium Lipid peroxidation |
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