Single-nucleotide polymorphism of human concentrative nucleoside transporter and mizoribine absorption in treating childhood-onset nephrotic syndrome

[Abstract] Mizoribine (MZR) is an immunosuppressant used to treat frequently relapsing nephrotic syndrome (FRNS). We often encounter patients in whom the serum MZR concentration is difficult to maintain. Even when the same dose is administered, concentrations in patients >= 10 years of age are often significantly lower than those in patients = 7 mg/kg/day) can fail to increase the serum concentrations in some patients with FRNS, leading to a relapse, and individual variation in MZR absorption may contribute to these issues. We previously linked a human concentrative nucleoside transporter (hCNT)2-related transport mechanism to MZR absorption. The MZR absorption significantly differed between patients expressing and those not expressing the hCNT2 gene. In the present study, we examined whether or not single nucleotide polymorphisms (SNPs) of the three hCNT genes are involved in the viability of MZR absorption. No significant associations between the serum MZR concentrations and SNPs of any of the three hCNT genes were evident. I also found no association between the MZR absorption and the SNPs of individual patients' hCNT genes considered in combination. Other absorptive or excretory mechanisms may therefore determine the maintenance of serum MZR concentrations.