Background: MDR1, a multidrug transporter, encodes a Pglycoprotein that regula tes the bioavailability of xenobiotics and is highly expressed at the blood-bra in-barrier. Two single nucleotide polymorphisms (SNPs) (e2...Background: MDR1, a multidrug transporter, encodes a Pglycoprotein that regula tes the bioavailability of xenobiotics and is highly expressed at the blood-bra in-barrier. Two single nucleotide polymorphisms (SNPs) (e21/ 2677[G/T/A] and e2 6/3435[C/T]) in the MDR1 gene can lead to differences in MDR1 expression and f un ction. Specific MDR1 alleles of the 2 SNPs are positively selected among ethnic Chinese but not in the white population. Objective: To determine whether specifi c 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. Set ting: Tertiary referral centers in Hong Kong. Subjects: One hundred eighty-five patients with PD and 206 control subjects. Interventions: The two SNPs were amp lified in a single multiplex polymerase chain reaction. Five other SNPs that spa n 100 kilobases of the gene were also analyzed. Main Outcome Measures: Haplotype s frequencies, degree of haplotype association with the disease status, and esti mated odds ratio for each haplotype with associated 95%confidence intervals. Re sults: In addition to 2677 G→T/A (exon 21) and 3435 C→T (exon 26), the other S NPs 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 containin g SNPs e21/2677 and e26/ 3435 were found to be significantly associated with ris k of PD. In particular, the 2677T-3435T haplotype was strongly associated with a reduced risk of PD (P < .001; χ2=14.521; odds ratio, 0.33; 95%confidence int erval, 0.19-0.59). Conclusions: An MDR1 haplotype containing SNPs e21/ 2677T an d e26/3435T protects against PD in ethnic Chinese, compatible with the observati on of a recent positive selection of the T alleles of these 2 SNPs in this ethni c population.展开更多
文摘Background: MDR1, a multidrug transporter, encodes a Pglycoprotein that regula tes the bioavailability of xenobiotics and is highly expressed at the blood-bra in-barrier. Two single nucleotide polymorphisms (SNPs) (e21/ 2677[G/T/A] and e2 6/3435[C/T]) in the MDR1 gene can lead to differences in MDR1 expression and f un ction. Specific MDR1 alleles of the 2 SNPs are positively selected among ethnic Chinese but not in the white population. Objective: To determine whether specifi c 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. Set ting: Tertiary referral centers in Hong Kong. Subjects: One hundred eighty-five patients with PD and 206 control subjects. Interventions: The two SNPs were amp lified in a single multiplex polymerase chain reaction. Five other SNPs that spa n 100 kilobases of the gene were also analyzed. Main Outcome Measures: Haplotype s frequencies, degree of haplotype association with the disease status, and esti mated odds ratio for each haplotype with associated 95%confidence intervals. Re sults: In addition to 2677 G→T/A (exon 21) and 3435 C→T (exon 26), the other S NPs 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 containin g SNPs e21/2677 and e26/ 3435 were found to be significantly associated with ris k of PD. In particular, the 2677T-3435T haplotype was strongly associated with a reduced risk of PD (P < .001; χ2=14.521; odds ratio, 0.33; 95%confidence int erval, 0.19-0.59). Conclusions: An MDR1 haplotype containing SNPs e21/ 2677T an d e26/3435T protects against PD in ethnic Chinese, compatible with the observati on of a recent positive selection of the T alleles of these 2 SNPs in this ethni c population.
