Effect of MDR1 haplotype on risk of Parkinson disease.
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.
Tan
Eng-King
EK
Department of Neurology, Singapore General Hospital, Singapore. gnrtek@sgh.com.sg
Chan
Daniel Kam-Yin
DK
Ng
Ping-Wing
PW
Woo
Jean
J
Teo
Y Y
YY
Tang
Kun
K
Wong
Li-Peng
LP
Chong
Samuel S
SS
Tan
Chris
C
Shen
Hui
H
Zhao
Yi
Y
Lee
Caroline G L
CG
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