The genetic polymorphisms of XPR1 and SCL34A3 are associated with Fanconi syndrome in Chinese patients of tumor-induced osteomalacia
The genetic polymorphisms of XPR1 and SCL34A3 are associated with Fanconi syndrome in Chinese patients of tumor-induced osteomalacia
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DOI：
10.1007/s40618-020-01371-w
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发表时间：
2020-07
影响因子：
5.4
通讯作者：
Yan Jiang;Xuewang Li;J. Feng;J. Feng;Mengtao Li;O. Wang;X. Xing;W. Xia
中科院分区：
文献类型：
--
作者：
Yan Jiang;Xuewang Li;J. Feng;J. Feng;Mengtao Li;O. Wang;X. Xing;W. Xia
目的肿瘤诱导的骨软化症（TIO）是一种获得性低磷血症，由肿瘤过度产生成纤维细胞生长因子23（FGF 23）引起。有文献报道TIO患者合并肾性范可尼综合征（FS），其发病机制尚不清楚。在这项研究中，我们调查了磷酸盐转运蛋白在肾近端小管和TIO与FS.MethodsWe招募30 TIO患者FS（TIO-FS），以及30 TIO患者（TIO-nonFS）没有任何尿液异常的年龄和性别相匹配之间的关联。结果TIO-FS组血磷水平明显低于TIO-nonFS组（0.44 ± 0.12vs.0.51 ± 0.07mmol/L，p< 0.05）;在SLC 34 A1、SLC 34 A3和XPR 1基因的16个SNP中，XPR 1中rs 148196667的GG/GC基因型和SLC 34 A3中rs35535797的AA/TA基因型与FS易感性降低相关。XPR 1中rs 148196667的G等位基因降低FS的风险。结论XPR 1和SCL 34 A3基因多态性与Fanconi综合征TIO患者相关。这为磷酸盐转运与肾近端小管一般功能的关系提供了新的见解。
PurposeTumor-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.MethodsWe 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.ResultsTIO-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.ConclusionsThe 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.