Gurung Resham L, Dorajoo Rajkumar, M Yiamunaa, Wang Ling, Liu Sylvia, Liu Jian-Jun, Shao Yi Ming, Chen Yuqing, Sim Xueling, Ang Keven, Subramaniam Tavintharan, Tang Wern Ee, Sum Chee Fang, Liu Jian-Jun, Lim Su Chi
Clinical Research Unit, Khoo Teck Puat Hospital, Singapore.
Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.
Clin Kidney J. 2021 Mar 26;14(11):2371-2376. doi: 10.1093/ckj/sfab067. eCollection 2021 Nov.
Chronic kidney disease (CKD) is common among people with type 2 diabetes (T2D), and increases the risk of kidney failure and cardiovascular diseases. Shorter leukocyte telomere length (LTL) is associated with CKD in patients with T2D. We previously reported single-nucleotide polymorphisms (SNPs) associated with LTL in an Asian population. In this study, we elucidated the association of these SNPs with CKD in patients with T2D using the Mendelian randomization (MR) approach.
The cross-sectional association of 16 LTL SNPs with CKD, defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m, was assessed among 4768 (1628 cases and 3140 controls) participants in the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in T2D and Diabetic Nephropathy cohorts. MR analysis was performed using the random-effect inverse-variance weighted (IVW) method, the weighted median, MR-Egger and Radial MR adjusted for age and sex-stratified by cohorts and ethnicity (Chinese and Malays), then meta-analyzed.
Genetically determined shorter LTL was associated with increased risk of CKD in patients with T2D (meta-IVW adjusted odds ratio= 1.51, 95% confidence interval 1.12-2.12, P=0.007, P =0.547). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (= 0.010, P=0.751).
Our findings suggest that genetically determined LTL is associated with CKD in patients with T2D. Further studies are warranted to elucidate the causal role of telomere length in CKD progression.
慢性肾脏病（CKD）在2型糖尿病（T2D）患者中很常见，并增加了肾衰竭和心血管疾病的风险。较短的白细胞端粒长度（LTL）与T2D患者的CKD相关。我们之前报道了亚洲人群中与LTL相关的单核苷酸多态性（SNP）。在本研究中，我们使用孟德尔随机化（MR）方法阐明了这些SNP与T2D患者CKD的关联。
在新加坡2型糖尿病大血管病变与微血管反应性及糖尿病肾病队列研究的4768名参与者（1628例病例和3140例对照）中，评估了16个LTL SNP与CKD（定义为估计肾小球滤过率<60 mL/min/1.73 m²）的横断面关联。使用随机效应逆方差加权（IVW）方法、加权中位数、MR-Egger和经年龄和性别调整的Radial MR进行MR分析，按队列和种族（中国人和马来人）分层，然后进行荟萃分析。
遗传决定的较短LTL与T2D患者CKD风险增加相关（荟萃分析IVW调整优势比=1.51，95%置信区间1.12-2.12，P=0.007，P异质性=0.547）。敏感性分析后获得了类似结果。MR-Egger分析（截距）表明没有水平多效性的证据（=0.010，P=0.751）。
我们的研究结果表明，遗传决定的LTL与T2D患者的CKD相关。有必要进一步研究以阐明端粒长度在CKD进展中的因果作用。
