MDR1, the blood–brain barrier transporter, is associated with Parkinson’s disease in ethnic Chinese

Pathogenic mutations in several genes-including α-synuclein, Parkin, UCH-L1 (ubiquitin-C terminal hydrolase-L1) and DJ-1-have previously been identified in rare monogenic forms of this disease showing autosomal dominant, autosomal recessive, or maternal transmission, with or without genetic anticipation. 2, 3 The more common, sporadic form of Parkinson's disease appears to result from an interaction between genetic and environmental factors. 4 Polymorphisms in several genes, including those implicated in familial forms of the disease such as α-synuclein 5 and Parkin, 6, 7 are also reported to be associated with the sporadic form. 8 Genetic susceptibility to sporadic Parkinson's disease was also found to be modulated by genes involved in xenobiotic management. The non-synonymous SNP e21/2677(G/T/A) was reported to change the efflux of digoxin in cells in vitro in one study, 27 but did not alter the efflux of several substrates in another study that used a different experimental system. 28 The synonymous SNP e26/3435(C/T) has variously been associated with differences in MDR1 protein expression and plasma drug concentration, 27, 29- 31 with drug induced side effects, 32 and with drug response. 33 Recently, these two SNPs and a third one, e1/-129(T/C), were examined in two case-control studies of approximately 100 patients with Parkinson's disease and matched normal controls. 34, 35 No statistical significance was found between any of these SNPs and Parkinson's disease.