Biochemical and Biophysical Research Communications
Regular ArticleProposed Schizophrenia-Related Gene Polymorphism: Expression of the Ser9Gly Mutant Human Dopamine D3Receptor with the Semliki Forest Virus System
Abstract
Homozygotes for aBalI polymorphism resulting in the Ser9Gly mutation in the human dopamine D3receptor gene are suggested to display a twofold higher risk of schizophrenia. The cDNAs for this mutant and the wildtype receptor were introduced into the pSFV1C vector and recombinant Semliki Forest virus particles generated. CHO cells infected with SFV-D3virus resulted in high level expression of recombinant receptor. Double infections with wildtype and Ser9Gly dopamine D3SFV stocks generated an artificial heterozygote in CHO cells. Receptor binding analysis of several structurally different dopamine D3ligands showed similar pharmacological properties for all compounds tested except for dopamine and the D3-selective ligand GR99841. A significantly higher dopamine binding afffinity for the Ser9Gly homozygote was detected. The heterozygote binding did not differ from the wildtype. However, both the homo- and heterozygote for Ser9Gly showed significantly higher binding activity for GR99841 compared to the D3wildtype.
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Pharmacogenomics in psychiatric diseases
2023, Pharmacogenomics: from Discovery to Clinical ImplementationPsychiatric disorders are the complex, devastating mental illnesses accompanied by changes in mood, behavior, and cognition. These disorders are a common cause of severe disability for an extended period and lead to socioeconomic liability. Apart from knowing the exact factors for its onset, its casual pathology remains an unsolved mystery. However, the recent developments in the field of neuroscience and psychiatry have been significant in revealing associated factors and consequent pathophysiology. The currently available treatment involves the use of antidepressants, mood stabilizers, and antipsychotics that are much more effective in generating a partial response in affected individuals. The polygenic nature of psychiatric disorders can be determined by the combinatorial result of known genetic variants through several combinations of associated factors, including polymorphism, chromosomal rearrangement, and copy number variation. Pharmacogenomic testing may prove to be quite useful in developing drug therapy for psychiatric disorders. Genome-wide studies and candidate gene approaches could offer vital insights into the neurobiological aspects of psychiatric diseases along with their proper management. The psychiatric pharmacogenomics method could improve precision in prescribing psychotropic drugs and analyze pharmacodynamics and pharmacokinetics of genes that affect the metabolism and response of these medications. This approach may help clinicians to design and prescribe suitable medications based on genomic information, thus improving the goal of clinical outcomes and identifying drugs that pose poor prognosis and fail in clinical trials.
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Akathisia and Restless Legs Syndrome: Solving the Dopaminergic Paradox
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