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

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Abstract

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 of SLC34A1, SLC34A3 and XPR1 genes 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 in SLC34A1, SLC34A3 and XPR1 genes, GG/GC genotypes of rs148196667 in XPR1 and AA/TA genotypes of rs35535797 in SLC34A3 were associated with a reduced susceptibility to have FS. The G allele of rs148196667 in XPR1 decreased the risk of FS. The GGAA haplotype in SLC34A3 and GCT haplotype in XPR1 were associated with a decreased risk for FS.

Conclusions

The polymorphisms of XPR1 and SCL34A3 are associated with TIO patients with Fanconi syndrome. It provides novel insight to the relationship of phosphate transportation and general functions of renal proximal tubules.

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Acknowledgements

This study was supported by “13th Five-Year” National Science and Technology Major Project for New Drugs (No: 2019ZX09734001), the National Key R&D Program of China (2018YFA0800801), the National Natural Science Foundation of China (No. 81970757), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Nos. 2017PT32020, 2018PT32001) and the CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-3-003). We are grateful to thank all patients for their involvements in this study. We wish to thank Dr. Wen-ting Gui and Cai-hua Li (Genesky Biotechnologies Inc., Shanghai, China) for technical support.

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Authors and Affiliations

  1. Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, 100730, China

    Y. Jiang, X. Li, J. Feng, M. Li, O. Wang, X.-P. Xing & W.-B. Xia

  2. Department of Endocrinology and Metabolism, South Campus, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201112, China

    J. Feng

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  1. Y. Jiang
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Jiang, Y., Li, X., Feng, J. et al. The genetic polymorphisms of XPR1 and SCL34A3 are associated with Fanconi syndrome in Chinese patients of tumor-induced osteomalacia. J Endocrinol Invest 44, 773–780 (2021). https://doi.org/10.1007/s40618-020-01371-w

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