Novel Mutation Detection of Regulatory Molecule Dopamine Gene Receptors (D1–D5) Encoding Analysis on Human Peripheral Blood Lymphocytes in Schizophrenia Patients

Abstract

There is much evidence which highlights the involvement of the dopamine system in the pathophysiology of schizophrenia. Recently, there have been reports of detected mutations in dopamine gene receptors in genomic DNA of schizophrenia. In this study, we attempt to determine whether there is mutation in encoding dopamine receptor. The PBMC was separated from whole blood by Ficoll-hypaque; the total cellular RNA was extracted and the cDNA was synthesized. This process followed by real-time PCR using primer pairs specific for five dopamine receptor mRNAs and β-actin as internal control. The results show the presence of all types of dopamine receptor types in lymphocytes. The mutational analysis of the obtained PCR products for the respective dopamine receptor fragments were analyzed by sequenced capillary system. The results presented in this study confirm the high frequency of mutations in dopamine gene receptor DRD5 in schizophrenia patients. Mutational amino acid changes in dopamine gene receptors of DR2, DR3, DR4 but not DR1 are also shown. In conclusion, this is the first report of such complete mutational analyses in all dopamine gene receptors. Moreover, we found new mutations and 80% frequency of mutations in DRD5. These data further strengthen the argument for the role of dopamine gene receptor mutations in the pathogenesis of schizophrenia.

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