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Association of a polymorphism in the ABCB1 gene with Parkinson's disease.

Journal article
Authors Marie Westerlund
Andrea Carmine Belin
Anna Anvret
Anna Håkansson
Hans Nissbrandt
Charlotta Lind
Olof Sydow
Lars Olson
Dagmar Galter
Published in Parkinsonism & related disorders
Volume 15
Issue 6
Pages 422-424
ISSN 1353-8020
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 422-424
Language en
Links dx.doi.org/10.1016/j.parkreldis.200...
Subject categories Pharmacology and Toxicology

Abstract

The ATP-binding cassette, sub-family B, member 1 (ABCB1) gene encoding the protein P-glycoprotein (P-gp) has been implicated in the pathophysiology of Parkinson's disease (PD) due to its role in regulating transport of endogenous molecules and exogenous toxins. In the present study, we analyzed the ABCB1 single nucleotide polymorphisms (SNPs) 1236C/T (exon 12), 2677G/T/A (exon 21) and 3435C/T (exon 26) in 288 Swedish PD patients and 313 control subjects and found a significant association of SNP 1236C/T with disease (p=0.0159; chi(2)=8.28), whereas the distributions of wild-type and mutated alleles were similar for 2677G/T/A and 3435C/T in patients and controls. Haplotype analysis revealed significant association of the 1236C-2677G haplotype with PD (p=0.026; chi(2)=4.955) and a trend towards association with disease of the 1236C-2677G-3435C haplotype (p=0.072; chi(2)=3.229). Altered ABCB1 and/or P-pg expression was recently shown in PD patients, and impaired drug efflux across barriers such as the gastrointestinal and nasal mucosal linings or the blood-brain barrier, might result in accumulation of drugs and/or endogenous molecules in toxic amounts, possibly contributing to disease. ABCB1 polymorphisms thus constitute an example of how genetic predisposition and environmental influences may combine to increase risk of PD.

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