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MDR1, the blood–brain barrier transporter, is associated with Parkinson’s disease in ethnic Chinese
  1. C G L Lee1,
  2. K Tang1,
  3. Y B Cheung2,
  4. L P Wong1,
  5. C Tan3,
  6. H Shen3,
  7. Y Zhao3,
  8. R Pavanni4,
  9. E J D Lee5,
  10. M-C Wong4,
  11. S S Chong6,
  12. E K Tan3
  1. 1Departments of Biochemistry, National University of Singapore, Singapore
  2. 2Biostatistics Unit, Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore
  3. 3Department of Neurology, Singapore General Hospital
  4. 4National Neuroscience Institute, Singapore
  5. 5Departments of Pharmacology, National University of Singapore
  6. 6Departments of Paediatrics, National University of Singapore
  1. Correspondence to:
 Dr Caroline G Lee
 Division of Medical Sciences, National Cancer Centre, Level 6, Lab 5, 11 Hospital Drive, Singapore 169610, Singapore; bchleecnus.edu.sg

https://doi.org/10.1136/jmg.2003.013003

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    Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease. It is characterised by bradykinesia, rigidity, resting tremor, and postural instability.1 It is a genetically heterogeneous disorder. 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-synuclein5 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. A meta-analysis of 84 association studies of 14 genes showed that polymorphisms in four genes are significantly associated with the disease.9 These genes are either responsible for xenobiotic metabolism, such as NAT210,11 and GSTT1,12 or may interact with environmental agents, such as monoamine oxidase (MAOB).13 Poor metaboliser alleles of the cytochrome P450 xenobiotic metabolism enzyme, CYP2D6, may also be associated with increased risk of Parkinson’s disease.14–20 Furthermore, there may be sex effects in the association of CYP2D6 mutant alleles with Parkinson’s disease.21

    These genetic association studies corroborate epidemiological studies, which have long suggested that Parkinson’s disease is associated with exposure to certain environmental xenobiotics. Although most of the specific agents remain to be identified, rural living, well water consumption, industrialisation, and herbicide/pesticide exposure have been implicated as potential risk factors.1,22,23

    Another category of genes that may influence susceptibility to Parkinson’s disease is the …

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    Footnotes

    • Conflicts of interest: none declared