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  Vol. 62 No. 3, March 2005 TABLE OF CONTENTS
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Effect of MDR1 Haplotype on Risk of Parkinson Disease

Eng-King Tan, MD; Daniel Kam-Yin Chan, MD; Ping-Wing Ng, MD; Jean Woo, MD; Y. Y. Teo, MSc; Kun Tang, BSc; Li-Peng Wong, Dip; Samuel S. Chong, PhD; Chris Tan, BSc; Hui Shen, PhD; Yi Zhao, MD, PhD; Caroline G. L. Lee, PhD

Arch Neurol. 2005;62:460-464.

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; {chi}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.


Author Affiliations: Department of Neurology, Singapore General Hospital (Drs Tan, Shen, and Zhao and Mr Tan); National Neuroscience Institute, Singapore (Dr Tan); SingHealth Research, Singapore (Dr Tan); Bankstown Lidcombe Hospital, The University of New South Wales, Bankstown, Australia (Dr Chan); United Christian Hospital, Hong Kong (Dr Ng); Department of Medicine and Therapeutics, The Chinese University of Hong Kong (Dr Woo); Department of Statistics, University of Oxford, Oxford, England (Mr Teo); Departments of Biochemistry (Mr Tang, Ms Wong, and Dr Lee) and Pediatrics (Dr Chong), National University of Singapore; Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Md (Dr Chong); and Division of Medical Sciences, National Cancer Centre, Singapore (Dr Lee).



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