Diagnostic and clinical significance of the titin fragment in urine of Duchenne muscular dystrophy patients
Diagnostic and clinical significance of the titin fragment in urine of Duchenne muscular dystrophy patients
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DOI：
10.1016/j.cca.2017.11.024
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发表时间：
2018-01-01
影响因子：
5
通讯作者：
Matsuo, Masafumi
中科院分区：
文献类型：
--
作者：
Awano, Hiroyuki;Matsumoto, Masaaki;Matsuo, Masafumi
杜氏肌营养不良症（DMD）是一种致命的儿童期进行性肌肉萎缩疾病。肌节中的肌苷被钙依赖性蛋白酶消化。为了探讨DMD的肌肉损伤，我们使用新开发的酶联免疫吸附测定试剂盒测定了尿中titin n端片段的浓度。尿titin浓度与肌酐（Cr）归一化。在日本一家医院共采集了113例3-29岁DMD患者的145份尿样。DMD患者正常尿titin浓度为965.8 +/- 1011.9（平均+/- SD） pmol/mg Cr。这比健康儿童（1.4 +/- 0.8 pmol/mg Cr）高出近700倍。DMD患者尿titin明显高于BMD患者，而BMD患者尿titin明显高于正常值。DMD患者尿titin随年龄增加而降低。最小组（3 ~ 7岁）和最大组（>= 16岁）尿titin中位浓度分别为1468.3和411.3 pmol/mg Cr，差异有统计学意义。尿titin浓度与血清肌酸激酶浓度显著相关，肌酸激酶是DMD最著名的生物标志物。尿中titin的n端片段有可能作为DMD的诊断和临床生物标志物。
Duchenne muscular dystrophy (DMD) is a fatal progressive muscle wasting disease of childhood. Titin in sarcomere is digested by calcium dependent protease. To explore muscle damage in DMD, the urinary concentrations of the N-terminal fragment of titin were determined using a newly developed enzyme linked immune sorbent assay kit. The urinary titin concentrations were normalized to creatinine (Cr). A total of 145 urine samples were obtained at a single Japanese hospital from 113 DMD patients aged 3-29 years. Normalized urinary titin concentration was 965.8 +/- 1011.9 (Mean +/- SD) pmol/mg Cr in patients with DMD. This was nearly 700-fold higher than healthy children (1.4 +/- 0.8 pmol/mg Cr). The concentration was significantly higher in DMD than in BMD patients who had significantly higher urinary titin than normal. Urinary titin in DMD patients tended to decrease with age. The median concentration of urinary titin in the youngest (aged 3-7 years) and oldest (aged >= 16 years) groups was 1468.3 and 411.3 pmol/mg Cr, respectively, with significant difference. Urinary concentration of titin Correlated significantly with serum creatine kinase concentration, the best-known biomarker of DMD. The N-terminal fragment of titin in urine has potential as a diagnostic and clinical biomarker for DMD.