Murdoch Children's Research Institute, Parkville, Australia.
Department of Paediatrics, The University of Melbourne, Parkville, Australia.
Clin Chem Lab Med. 2021 Mar 15;59(7):1279-1288. doi: 10.1515/cclm-2021-0059. Print 2021 Jun 25.
Children with very short telomeres commonly develop bone marrow failure and other severe diseases. Identifying the individuals with short telomeres can improve outcome of bone marrow transplantation, with accurate diagnosis requiring the use of age-matched reference intervals (RIs). This study aimed to establish RIs for telomere length (TL) in children using three commonly used methods for TL measurement.
Healthy children aged 30 days to 18 years were recruited for assessment using age as a continuous variable. Venous blood samples were collected and leukocyte TL was measured using terminal restriction fragment (TRF) analysis, quantitative PCR (QPCR) and flow cytometry with fluorescence hybridization (Flow-FISH). Fractional polynomial model and quantile regression were performed to generate continuous RIs. Factors that might contribute to variation in TL, such as gender, were also examined.
A total of 212 samples were analyzed. Continuous RIs are presented as functions of age. TRF analysis and QPCR showed significant negative correlation between TL and age (r=-0.28 and r=-0.38, p<0.001). In contrast, Flow-FISH showed no change in TL with age (r=-0.08, p=0.23). Gender did not have significant influence on TL in children.
This study provides three options to assess TL in children by establishing method-specific continuous RIs. Choosing which method to use will depend on several factors such as amount and type of sample available and required sensitivity to age-related change.
端粒极短的儿童通常会出现骨髓衰竭和其他严重疾病。识别端粒较短的个体可以改善骨髓移植的预后，而准确的诊断需要使用与年龄匹配的参考区间（RIs）。本研究旨在使用三种常用的端粒长度（TL）测量方法为儿童建立 TL 的 RI。
招募了年龄在 30 天至 18 岁之间的健康儿童，作为连续变量进行评估。采集静脉血样本，使用末端限制性片段（TRF）分析、定量 PCR（QPCR）和荧光杂交流式细胞术（Flow-FISH）测量白细胞 TL。采用分数多项式模型和分位数回归生成连续 RI。还检查了可能导致 TL 变化的因素，如性别。
共分析了 212 个样本。连续 RI 呈现为年龄的函数。TRF 分析和 QPCR 显示 TL 与年龄呈显著负相关（r=-0.28 和 r=-0.38，p<0.001）。相比之下，Flow-FISH 显示 TL 随年龄变化无变化（r=-0.08，p=0.23）。性别对儿童 TL 无显著影响。
本研究通过建立特定方法的连续 RI，为评估儿童 TL 提供了三种选择。选择使用哪种方法将取决于几个因素，例如可用样本的数量和类型以及对年龄相关变化的敏感性要求。
