School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
University of Minnesota Medical School, University of Minnesota, Minneapolis, MN, USA.
Rheumatology (Oxford). 2020 May 1;59(5):940-947. doi: 10.1093/rheumatology/kez524.
To evaluate the telomere length (TL) in patients with RA relative to that in controls and to test whether TL is causally associated with risk of RA.
Systematic review and meta-analysis of relevant literature was conducted to evaluate the association between TL and RA. Standardized mean differences with 95% CIs of TL in RA patients relative to controls were pooled using fixed or random-effects models. TL-related single-nucleotide polymorphisms were selected from a genome-wide association study of 37 684 individuals, and summary statistics of RA were obtained from a genome-wide association study meta-analysis including 14 361 RA patients and 43 923 controls. Mendelian randomization was performed using the inverse-variance weighted, weighted-median and likelihood-based methods. Sensitivity analyses were performed to test the robustness of the association.
In the meta-analysis of 911 RA patients and 2498 controls, we found that patients with RA had a significantly shorter TL compared with controls (standardized mean differences = -0.50; 95% CI -0.88, -0.11; P = 0.012). In the Mendelian randomization analysis, we found that genetically predicted longer TL was associated with a reduced risk of RA [odds ratio = 0.68; 95% CI 0.54, 0.86; P = 0.002 using the inverse-variance weighted method]. Sensitivity analyses using alternative Mendelian randomization approaches yielded similar findings, suggesting the robustness of the causal association.
Our study provides evidence for a negative causal association of TL with risk of RA. Further studies are warranted to elucidate the underlying mechanism for the role of telomeres in the development of RA.
评估类风湿关节炎（RA）患者的端粒长度（TL）与对照者相比的差异，并检验 TL 是否与 RA 的发病风险存在因果关系。
系统检索并分析相关文献，评估 TL 与 RA 之间的关联。采用固定或随机效应模型，对 RA 患者 TL 与对照者 TL 的标准化均数差值（SMD）及其 95%置信区间（CI）进行合并。从一项包含 37684 例个体的全基因组关联研究中选择与 TL 相关的单核苷酸多态性（SNP），并从一项包含 14361 例 RA 患者和 43923 例对照者的全基因组关联研究荟萃分析中获得 RA 的汇总统计数据。采用逆方差加权、加权中位数和似然比法进行孟德尔随机化分析。进行敏感性分析以检验关联的稳健性。
纳入 911 例 RA 患者和 2498 例对照者的荟萃分析显示，与对照者相比，RA 患者的 TL 显著缩短（SMD = -0.50；95%CI -0.88，-0.11；P = 0.012）。孟德尔随机化分析显示，遗传预测的较长 TL 与 RA 发病风险降低相关[比值比（OR）= 0.68；95%CI 0.54，0.86；P = 0.002，采用逆方差加权法]。采用替代孟德尔随机化方法进行的敏感性分析得出了相似的结果，提示该因果关联具有稳健性。
本研究为 TL 与 RA 发病风险之间存在负向因果关联提供了证据。需要进一步的研究阐明端粒在 RA 发病机制中的作用机制。
