The genetic polymorphisms of XPR1 and SCL34A3 are associated with Fanconi syndrome in Chinese patients of tumor-induced osteomalacia

Purpose Tumor-induced osteomalacia (TIO) is an acquired form of hypophosphatemia caused by tumors with excess production of fibroblast growth factor 23 (FGF23). Some reports showed that TIO patients had renal Fanconi syndrome (FS) with unidentified mechanism. In this study, we investigated the association between genetic polymorphisms of phosphate transporters in renal proximal tubules and TIO with FS. Methods We recruited 30 TIO patients with FS (TIO-FS) as well as 30 TIO patients (TIO-nonFS) without any urine abnormalities matched by age and gender. We collected clinical manifestations and conducted targeted sequencing ofSLC34A1,SLC34A3and XPR1genes and the association analysis between variants in TIO with FS and phenotypes. Results TIO-FS group had lower levels of serum phosphate (0.44 +/- 0.12 vs. 0.51 +/- 0.07 mmol/L,p < 0.05) than TIO-nonFS group. Among the 16 SNPs inSLC34A1,SLC34A3and XPR1genes, GG/GC genotypes of rs148196667 inXPR1and AA/TA genotypes of rs35535797 inSLC34A3were associated with a reduced susceptibility to have FS. The G allele of rs148196667 inXPR1decreased the risk of FS. The GGAA haplotype inSLC34A3and GCT haplotype inXPR1were associated with a decreased risk for FS. Conclusions The polymorphisms ofXPR1andSCL34A3are associated with TIO patients with Fanconi syndrome. It provides novel insight to the relationship of phosphate transportation and general functions of renal proximal tubules.