title: Effect of MDR1 haplotype on risk of Parkinson disease.
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.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Tertiary referral centers in Hong Kong.
  
  
  METHODS
  One hundred eighty-five patients with PD and 206 control subjects.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Neurology, Singapore General Hospital, Singapore. gnrtek@sgh.com.sg
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
authors.forename: Daniel Kam-Yin
authors.initials: DK
authors.lastname: Chan
authors.forename: Ping-Wing
authors.initials: PW
authors.lastname: Ng
authors.forename: Jean
authors.initials: J
authors.lastname: Woo
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: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Caroline G L
authors.initials: CG
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D019450:Genes, MDR / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors