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.
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.
Authors: Chava Kimchi-Sarfaty; Andrew H Marple; Shiri Shinar; Avraham M Kimchi; David Scavo; M Isabella Roma; In-Wha Kim; Adam Jones; Mili Arora; John Gribar; David Gurwitz; Michael M Gottesman Journal: Pharmacogenomics Date: 2007-01 Impact factor: 2.533
Authors: José A G Agúndez; Antonio Luengo; Oscar Herráez; Carmen Martínez; Hortensia Alonso-Navarro; Félix Javier Jiménez-Jiménez; Elena García-Martín Journal: Neuromolecular Med Date: 2007-11-06 Impact factor: 3.843
Authors: Katja Zschiedrich; Inke R König; Norbert Brüggemann; Norman Kock; Meike Kasten; Klaus L Leenders; Vladimir Kostić; Peter Vieregge; Andreas Ziegler; Christine Klein; Katja Lohmann Journal: J Neurol Date: 2009-01-29 Impact factor: 4.849
Authors: Sarah E Lacher; Julia N Gremaud; Kasse Skagen; Emily Steed; Rachel Dalton; Kent D Sugden; Fernando Cardozo-Pelaez; Catherine M T Sherwin; Erica L Woodahl Journal: J Pharmacol Exp Ther Date: 2013-12-02 Impact factor: 4.030