title: Analysis of MDR1 haplotypes in Parkinson's disease in a white population.
abstract: The MDR1 multidrug transporter is important in regulating environmental xenobiotics and hence may play a causative role in Parkinson's disease (PD). MDR1 haplotype comprising 2677 G > T/A and 3435 C > T may be protective against PD. Using a case control methodology, we investigated the association of MDR1 haplotypes (single nucleotide polymorphisms (SNPs) 2677 G > T/A and 3435 C > T) in a Polish PD population. Seven SNPs, extending from the promoter to exon 28 of the MDR1 gene in 158 PD patients and 139 healthy controls were evaluated. Specifically we examined the association of haplotypes containing SNPs 2677 G > T/A and 3435 C > T and risk of PD. The multivariate logistic regression model was used to evaluate the effects of the covariates on the phenotypes. Haplotypes' frequencies were estimated using the Expectation-Maximization algorithm. The frequency of each individual SNPs; -41 A > G (intron -1), -145 C > G (exon 1), -129 T > C (exon 1), 1236 T > C (exon 12), 2677 G > T/A (exon 21), 3435 C > T (exon 26), and 4036 A > G (exon 28) did not differ between PD and controls. However, there was a trend towards significance in PD patients having the haplotype 2677G-3435C (p < 0.09, chi-square 2.85, odds ratio 0.25, 95% CI 0.06-1.08). Haplotype constructs of the other loci did not differ significantly between the two groups. There was a weak protective effect of the haplotype 2677G-3435C in our white population. However, the MDR1 haplotypes did not generally modulate the risk of PD.
authors.affiliation: Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. gnrtek@sgh.com.sg
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
authors.forename: Marek
authors.initials: M
authors.lastname: Drozdzik
authors.forename: Monika
authors.initials: M
authors.lastname: Bialecka
authors.forename: Krystyna
authors.initials: K
authors.lastname: Honczarenko
authors.forename: Gabriela
authors.initials: G
authors.lastname: Klodowska-Duda
authors.forename: Y Y
authors.initials: YY
authors.lastname: Teo
authors.forename: Kun
authors.initials: K
authors.lastname: Tang
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Wong
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Chong
authors.forename: Chris
authors.initials: C
authors.lastname: Tan
authors.forename: Kenneth
authors.initials: K
authors.lastname: Yew
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Caroline Gl
authors.initials: CG
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D019450:Genes, MDR / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D044465:White People