Functional Analysis of Human Sodium-Phosphate Transporter 4 (NPT4/SLC17A3) Polymorphisms

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  • Jutabha Promsuk
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan
  • Anzai Naohiko
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan
  • Kimura Toru
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan
  • Taniguchi Atsuo
    Institute of Rheumatology, Tokyo Women’s Medical University, Japan
  • Urano Wako
    Institute of Rheumatology, Tokyo Women’s Medical University, Japan
  • Yamanaka Hisashi
    Institute of Rheumatology, Tokyo Women’s Medical University, Japan
  • Endou Hitoshi
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan
  • Sakurai Hiroyuki
    Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Japan

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Abstract

We analyzed the functional properties of five nonsynonymous single nucleotide polymorphisms (SNPs) in the sodium-phosphate transporter NPT4 gene (SLC17A3) using the Xenopus oocyte expression system. NPT4 variants carrying SNP V257F, G279R, or P378L exhibited reduced transport of [14C]para-aminohippurate, [3H]bumetanide, [3H]estrone sulfate, and [14C]urate, when each variant clone was expressed in the plasma membrane of oocytes. This study suggests the possibility that the genetic variation of NPT4 contributes to inter-individual differences in disposition of anionic drugs such as diuretics as well as certain endogenous organic anions such as urate.

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