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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Functional analysis of human organic cation transporter OCT3 (SLC22A3) polymorphisms
Takeshi Sakata1, Naohiko Anzai, Toru Kimura
1Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Journal of Pharmacological Sciences
|June 22, 2010
Summary
Genetic variations in the organic cation transporter 3 (OCT3) gene affect its function. These OCT3 variants may influence drug metabolism and disease risk, impacting conditions like hypertension.
Area of Science:
- Pharmacogenomics
- Molecular biology
- Biochemistry
Background:
- The organic cation transporter 3 (OCT3) plays a crucial role in transporting endogenous organic cations and xenobiotics.
- Single nucleotide polymorphisms (SNPs) in the OCT3 gene (SLC22A3) can alter transporter function and influence drug response and disease susceptibility.
Purpose of the Study:
- To investigate the functional impact of five OCT3 gene SNPs that result in amino acid changes.
- To determine how these OCT3 variants affect the transport of substrates like histamine and MPP+.
Main Methods:
- Transient expression system was employed to analyze the functional properties of OCT3 variants.
- Uptake assays using [(3)H]histamine and [(3)H]MPP(+) were performed.
- Protein expression levels and localization in transfected cells were assessed.
Main Results:
- Three specific OCT3 SNPs (A116S, T400I, A439V) demonstrated significantly reduced uptake of both [(3)H]histamine and [(3)H]MPP(+).
- Despite reduced transport activity, the protein expression of these variants was detected in the plasma membrane of transfected cells.
Conclusions:
- The identified OCT3 variants can impair the transporter's function, leading to reduced clearance of organic cations.
- These functional OCT3 variants may contribute to inter-individual variability in cationic drug disposition.
- Altered OCT3 function could be implicated in the pathogenesis of diseases such as hypertension, allergic diseases, and neuropsychiatric disorders.
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