法布里病的衰老：端粒长度、端粒酶活性和肾脏疾病的作用。

Aging in Fabry Disease: Role of Telomere Length, Telomerase Activity, and Kidney Disease.

机构信息

Department of Internal Medicine, General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia,

Institute of Oncology Ljubljana, Department of Molecular Diagnostics, Ljubljana, Slovenia.

出版信息

Nephron. 2020;144(1):5-13. doi: 10.1159/000502909. Epub 2019 Sep 11.

DOI:10.1159/000502909

PMID:31509825

Abstract

INTRODUCTION

The lifespan of patients with Fabry disease (FD) is shorter than that seen in the general population. Leukocyte telomere length (LTL) and telomerase activity (TA) are potential markers of biologic aging. The aim of the current study was to determine the LTL and TA in FD patients and to assess the correlation between LTL and TA and renal involvement.

METHODS

We included 33 FD patients and 66 healthy matched controls. LTL and TA were measured using a quantitative PCR assay and gene expression assay. FD patients were stratified by renal function (estimated glomerular filtration rate [eGFR] higher or lower than 60 mL/min/1.73 m2) and proteinuria (urine protein creatinine ratio higher or lower than 0.5 g/g).

RESULTS

LTL was significantly shorter (0.69 vs. 0.73, p = 0.015) and TA significantly higher (1.55 vs. 1.19, p = 0.047) in FD patients compared to controls. Males with FD had significantly shorter LTL (p = 0.020) and lower, but non-significant, TA compared to male controls (p = 0.333). Female FD patients had similar LTL (p = 0.285) but significantly higher TA compared to female controls (p = 0.005). LTL was not influenced by eGFR, but TA was significantly lower in the low eGFR group (p = 0.003).

CONCLUSIONS

FD patients have significantly shorter LTL, but significantly higher TA compared to healthy controls. Increased TA activity in FD patients could be the compensation mechanism to prevent LTL decrease (and accelerated ageing), which seems to be exhausted at the advanced stage of renal disease.

摘要

简介

法布里病（FD）患者的寿命短于普通人群。白细胞端粒长度（LTL）和端粒酶活性（TA）是生物衰老的潜在标志物。本研究旨在确定 FD 患者的 LTL 和 TA，并评估 LTL 和 TA 与肾脏受累之间的相关性。

方法

我们纳入了 33 名 FD 患者和 66 名健康匹配对照。使用定量 PCR 检测和基因表达检测来测量 LTL 和 TA。根据肾功能（估计肾小球滤过率[eGFR]高于或低于 60 mL/min/1.73 m2）和蛋白尿（尿蛋白肌酐比高于或低于 0.5 g/g）对 FD 患者进行分层。

结果

与对照组相比，FD 患者的 LTL 明显更短（0.69 比 0.73，p = 0.015），TA 明显更高（1.55 比 1.19，p = 0.047）。与男性对照组相比，FD 男性患者的 LTL 明显更短（p = 0.020），TA 较低，但无统计学意义（p = 0.333）。FD 女性患者的 LTL 相似（p = 0.285），但 TA 明显高于女性对照组（p = 0.005）。LTL 不受 eGFR 影响，但低 eGFR 组的 TA 明显降低（p = 0.003）。