Effect of MDR1 haplotype on risk of Parkinson disease
Tan, E.-K. Chan, D.K.-Y. Ng, P.-W. Woo, J. Teo, Y.Y. Tang, K. Wong, L.-P. Chong, S.S. Tan, C. Shen, H.
Tan, E.-K.
Chan, D.K.-Y.
Ng, P.-W.
Woo, J.
Teo, Y.Y.
Tang, K.
Wong, L.-P.
Tan, C.
Shen, H.
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Abstract
Background: MDR1, a multidrug transporter, encodes a P-glycoprotein that regulates the bioavailability of xenobiotics and is highly expressed at the blood-brain-barrier. Two single nucleotide polymorphisms (SNPs) (e21/ 2677[G/T/A] and e26/3435[C/T]) in the MDR1 gene can lead to differences in MDR1 expression and function. Specific MDR1 alleles of the 2 SNPs are positively selected among ethnic Chinese but not in the white population. Objective: To determine whether specific haplotypes formed by SNPs e21/2677 and e26/3435 may protect against Parkinson disease (PD) among ethnic Chinese in Hong Kong. Design: Case-control study. Setting: Tertiary referral centers in Hong Kong. Subjects: One hundred eighty-five patients with PD and 206 control subjects. Interventions: The two SNPs were amplified in a single multiplex polymerase chain reaction. Five other SNPs that span 100 kilobases of the gene were also analyzed. Main Outcome Measures: Haplotypes frequencies, degree of haplotype association with the disease status, and estimated odds ratio for each haplotype with associated 95% confidence intervals. Results: In addition to 2677 G→T/A (exon 21) and 3435 C→T (exon 26), the other SNPs that were analyzed were -41 A→G (intron-1), -145 C→G (exon 1), -129 T→C (exon 1), 1236 T→C (exon 12), and 4036 A→G (exon 28). Haplotypes containing SNPs e21/2677 and e26/ 3435 were found to be significantly associated with risk of PD. In particular, the 2677T-3435T haplotype was strongly associated with a reduced risk of PD (P<.001; χ 2 = 14.521; odds ratio, 0.33; 95% confidence interval, 0.19-0.59). Conclusions: An MDR1 haplotype containing SNPs e21/ 2677T and e26/3435T protects against PD in ethnic Chinese, compatible with the observation of a recent positive selection of the T alleles of these 2 SNPs in this ethnic population.
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Source Title
Archives of Neurology
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Series/Report No.
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Date
2005-03
DOI
10.1001/archneur.62.3.460
Type
Article