XPR1 和 SCL34A3 的基因多态性与中国人肿瘤相关性骨软化症所致的范可尼综合征有关。

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

机构信息

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.

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

出版信息

J Endocrinol Invest. 2021 Apr;44(4):773-780. doi: 10.1007/s40618-020-01371-w. Epub 2020 Jul 28.

DOI:10.1007/s40618-020-01371-w

PMID:32725396

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.

摘要

目的

肿瘤性骨软化症（TIO）是一种由成纤维细胞生长因子 23（FGF23）过度产生的肿瘤引起的获得性低磷血症。一些报道显示，TIO 患者存在机制不明的肾范可尼综合征（FS）。本研究旨在探讨近端肾小管磷酸盐转运体的遗传多态性与伴有 FS 的 TIO 之间的关系。

方法

我们招募了 30 名伴有 FS 的 TIO 患者（TIO-FS）以及 30 名年龄和性别相匹配的无任何尿液异常的 TIO 患者（TIO-nonFS）。我们收集了临床症状，并对 SLC34A1、SLC34A3 和 XPR1 基因进行了靶向测序，并对伴有 FS 的 TIO 患者的表型与变体之间的关联进行了分析。

结果

TIO-FS 组的血清磷酸盐水平（0.44 ± 0.12 vs. 0.51 ± 0.07 mmol/L，p < 0.05）低于 TIO-nonFS 组。在 SLC34A1、SLC34A3 和 XPR1 基因中的 16 个 SNP 中，XPR1 基因中的 rs148196667 的 GG/GC 基因型和 SLC34A3 基因中的 rs35535797 的 AA/TA 基因型与 FS 的易感性降低有关。XPR1 基因中的 rs148196667 的 G 等位基因降低了 FS 的风险。SLC34A3 中的 GGAA 单倍型和 XPR1 中的 GCT 单倍型与 FS 的风险降低有关。