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Published on: April 4, 2018
Functional analysis of human sodium-phosphate transporter 4 (NPT4/SLC17A3) polymorphisms
Promsuk Jutabha1, Naohiko Anzai, Toru Kimura
1Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, Japan.
Genetic variations in the NPT4 gene (SLC17A3) affect the transport of drugs and urate. These NPT4 functional changes may explain differences in how individuals process anionic compounds.
Area of Science:
- Pharmacogenomics
- Molecular Biology
- Renal Physiology
Background:
- The sodium-phosphate transporter NPT4 (SLC17A3) plays a role in the transport of organic anions.
- Genetic variations, specifically nonsynonymous single nucleotide polymorphisms (SNPs), can alter protein function.
Purpose of the Study:
- To investigate the functional impact of five nonsynonymous SNPs in the NPT4 gene.
- To determine if NPT4 genetic variations affect the transport of specific anionic substrates.
Main Methods:
- Xenopus oocyte expression system was utilized to express NPT4 variants.
- Transport assays were performed using radiolabeled substrates: para-aminohippurate, bumetanide, estrone sulfate, and urate.
Main Results:
- NPT4 variants V257F, G279R, and P378L showed significantly reduced transport activity.
- The reduced transport was observed for all tested anionic substrates, including drugs and urate.
Conclusions:
- Genetic variations in NPT4 can impair its transport function.
- NPT4 genetic polymorphisms may contribute to inter-individual variability in the disposition of anionic drugs and endogenous compounds like urate.
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