Genotype and smoking history affect risk of levodopa-induced dyskinesias in Parkinson's disease

Authors

  • Judith A. Strong PhD,

    Corresponding author
    1. Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Current affiliation:
    1. Department of Anesthesia, University of Cincinnati, Cincinnati, Ohio, USA
    • Department of Anesthesia, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267
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  • Arif Dalvi MD,

    1. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Current affiliation:
    1. Department of Neurology, University of Chicago, Chicago, Illinois, USA
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  • Fredy J. Revilla MD,

    1. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Alok Sahay MD,

    1. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Frederick J. Samaha MD,

    1. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Jeffrey A. Welge PhD,

    1. Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Jianhua Gong PhD,

    1. Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Current affiliation:
    1. Food Research Program, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada
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  • Maureen Gartner RN, MEd,

    1. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Xia Yue BS,

    1. Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Lei Yu PhD

    1. Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Current affiliation:
    1. Department of Zoology, University of Guelph, Guelph, Ontario, Canada
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Abstract

Parkinson's disease (PD) patients vary widely in their response to levodopa treatment, and this variation may be partially genetic in origin. We determined whether particular dopamine and opioid receptor polymorphisms were associated with risk of earlier onset of dyskinesia side effects during levodopa therapy. Smoking status was also examined. The 92 subjects were recruited from the movement disorders clinic of a neurology practice associated with a medical school. All were adult-onset PD patients who had been taking levodopa at least 5 years and/or had developed levodopa-induced dyskinesia. Carrying the G-allele of the A118G single nucleotide coding region polymorphism of the mu opioid receptor, as well as a history of never smoking, were independently associated with increased risk of earlier onset of dyskinesia (P = 0.05 and 0.02, respectively). One genotype of the D2 dopamine receptor intronic dinucleotide repeat polymorphism (14 repeats/15 repeats, with frequency of 6%) was also associated with earlier dyskinesia (P = 0.003). History of smoking has previously been associated with reduced risk of developing PD. Our results suggest that smoking history may also influence the response to levodopa, with contribution comparable to those of individual genes including the mu opioid receptor and D2 dopamine receptor. © 2006 Movement Disorder Society

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