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Hypomethylation of the serotonin receptor type-2A Gene (HTR2A) at T102C polymorphic site in DNA derived from the saliva of patients with schizophrenia and bipolar disorder

Authors

  • Mohammad Ghadirivasfi,

    1. Mental Health Research Center, Department of Psychiatry, Tehran University of Medical Sciences, Tehran, Iran
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  • Shabnam Nohesara,

    1. Mental Health Research Center, Department of Psychiatry, Tehran University of Medical Sciences, Tehran, Iran
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  • Hamid-Reza Ahmadkhaniha,

    1. Mental Health Research Center, Department of Psychiatry, Tehran University of Medical Sciences, Tehran, Iran
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  • Mohammad-Reza Eskandari,

    1. Laboratory of Nutrition and Metabolism at BIDMC, Harvard Medical School, Boston, Massachusetts
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  • Siavash Mostafavi,

    1. Department of Biological Sciences, University of Massachusetts at Lowell, Massachusetts
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  • Sam Thiagalingam,

    Corresponding author
    1. Department of Medicine (Biomedical Genetics, Genetics & Genomics) and Genome Science Institute, Boston, Massachusetts
    2. Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts
    • Boston University School of Medicine (L320), 72 East Concord Street, Boston, MA 02118.
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  • Hamid Mostafavi Abdolmaleky

    Corresponding author
    1. Mental Health Research Center, Department of Psychiatry, Tehran University of Medical Sciences, Tehran, Iran
    2. Laboratory of Nutrition and Metabolism at BIDMC, Harvard Medical School, Boston, Massachusetts
    3. Department of Medicine (Biomedical Genetics, Genetics & Genomics) and Genome Science Institute, Boston, Massachusetts
    • Boston University School of Medicine (L320), 72 East Concord Street, Boston, MA 02118.
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  • Sam Thiagalingam and Hamid Mostafavi Abdolmaleky contributed equally to this work.

  • How to cite this article as follows: Ghadirivasfi M, Nohesara S, Ahmadkhaniha H-R, Eskandari M-R, Mostafavi S, Thiagalingam S, Abdolmaleky HM. 2011. Hypomethylation of the Serotonin Receptor Type-2A Gene (HTR2A) at T102C Polymorphic Site in DNA Derived From the Saliva of Patients With Schizophrenia and Bipolar Disorder. Am J Med Genet Part B 156:536–545.

Abstract

Several lines of evidence indicate that dysfunction of serotonin signaling and HTR2A receptor are involved in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BD). DNA methylation of HTR2A at T102C polymorphic site influences HTR2A expression and aberrant DNA methylation of HTR2A promoter was reported in postmortem brain of patients with SCZ and BD. Hypothesizing that the brain's epigenetic alteration of HTR2A may also exist in peripheral tissues that can be used as a diagnostic/therapeutic biomarker, we analyzed HTR2A promoter DNA methylation in DNA extracted from the saliva of patients with SCZ and BD, and their first degree relatives versus normal controls. Bisulfite sequencing was used to screen DNA methylation status of the HTR2A promoter CpGs and qMSP was used to quantify the degree of cytosine methylation at differentially methylated sites. Most of the cytosines of the HTR2A promoter were unmethylated. However, CpGs of the −1438A/G polymorphism site, −1420 and −1223 were >95% methylated. The CpG at T102C polymorphic site and neighboring CpGs were ∼70% methylated both in the patients and controls. qMSP analysis revealed that the cytosine of the T102C polymorphic site was significantly hypo-methylated in SCZ, BD, and their first degree relatives compared to the controls. Cytosine methylation of HTR2A at T102C polymorphic site in DNA derived from the saliva can potentially be used as a diagnostic, prognostic, and/or therapeutic biomarker in SCZ and BD. However, these preliminary observations need to be replicated in other populations with a larger sample size to be considered for clinical applications. © 2011 Wiley-Liss, Inc.

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