title: Association of a polymorphism in the ABCB1 gene with Parkinson's disease.
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.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. marie.westerlund@ki.se
authors.forename: Marie
authors.initials: M
authors.lastname: Westerlund
authors.forename: Andrea Carmine
authors.initials: AC
authors.lastname: Belin
authors.forename: Anna
authors.initials: A
authors.lastname: Anvret
authors.forename: Anna
authors.initials: A
authors.lastname: Håkansson
authors.forename: Hans
authors.initials: H
authors.lastname: Nissbrandt
authors.forename: Charlotta
authors.initials: C
authors.lastname: Lind
authors.forename: Olof
authors.initials: O
authors.lastname: Sydow
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
authors.forename: Dagmar
authors.initials: D
authors.lastname: Galter
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1