Hereditary variations in monoamine oxidase as a risk factor for Parkinson's disease

Authors

  • Gokhan S. Hotamisligil,

    1. Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital, Charlestown, Massachusetts
    2. Department of Microbiology and Molecular Genetics, and Neuroscience Program, Harvard Medical School, Boston, Massachusetts
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  • A. Sule Girmen,

    1. Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital, Charlestown, Massachusetts
    2. Department of Microbiology and Molecular Genetics, and Neuroscience Program, Harvard Medical School, Boston, Massachusetts
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  • J. Stephen Fink,

    1. Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital, Charlestown, Massachusetts
    2. Department of Microbiology and Molecular Genetics, and Neuroscience Program, Harvard Medical School, Boston, Massachusetts
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  • Elizabeth Tivol,

    1. Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital, Charlestown, Massachusetts
    2. Department of Microbiology and Molecular Genetics, and Neuroscience Program, Harvard Medical School, Boston, Massachusetts
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  • Christo Shalish,

    1. Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital, Charlestown, Massachusetts
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  • James Trofatter,

    1. Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital, Charlestown, Massachusetts
    2. Department of Microbiology and Molecular Genetics, and Neuroscience Program, Harvard Medical School, Boston, Massachusetts
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  • John Baenziger,

    1. Departments of Psychiatry and Pathology, Alcohol Research Center, Indiana University Medical Center, Indianapolis, Indiana
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  • Shirley Diamond,

    1. Department of Neurology, School of Medicine, University of California, Los Angeles, California, U.S.A.
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  • Charles Markham,

    1. Department of Neurology, School of Medicine, University of California, Los Angeles, California, U.S.A.
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  • Jack Sullivan,

    1. Departments of Psychiatry and Pathology, Alcohol Research Center, Indiana University Medical Center, Indianapolis, Indiana
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  • John Growdon,

    1. Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital, Charlestown, Massachusetts
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  • Xandra O. Breakefield

    Corresponding author
    1. Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital, Charlestown, Massachusetts
    • Massachusetts General Hospital East, Building 149, 13th Street, Charlestown, MA 02129, U.S.A.
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Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder caused by loss of dopaminergic neurons in the brainstem. Recent studies suggest that several genes may have a role in determining individual susceptibility to this disease, and the degradative enzyme monoamine oxidase (MAO) has been implicated in the disease process. Wide differences in activity levels for both forms of this enzyme (MAO-A and MAO-B) exist in the human population, and levels of both are genetically determined. Here we have compared the frequency of haplotypes at the MAOA and MAOB loci on the X chromosome in 91 male patients with PD and 129 male controls. Alleles were marked using two restriction fragment length polymorphisms (RFLPs), a (GT)n repeat in the MAOA locus, and a (GT)n repeat in the MAOB locus. One particular haplotype marked by the RFLP's at MAOA was three times more frequent in patients with PD as compared with controls, and the overall distribution of these alleles was significantly different (p =0.03) between these two groups. Another MAOA haplotype was about threefold more common in controls than in patients with PD (p = 0.005). No associations were observed between individual MAOB alleles and the disease state, but the frequency distribution for all alleles was significantly different in the two populations (p = 0.046). These findings support the idea that the MAO genes may be among the herediatary factors that influence susceptibility of individuals to PD.

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