Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 26;14(11):2371-2376.
doi: 10.1093/ckj/sfab067. eCollection 2021 Nov.

Association of leukocyte telomere length with chronic kidney disease in East Asians with type 2 diabetes: a Mendelian randomization study

Resham L Gurung  1 , Rajkumar Dorajoo  2 , Yiamunaa M  1 , Ling Wang  2 , Sylvia Liu  1 , Jian-Jun Liu  1 , Yi Ming Shao  1 , Yuqing Chen  3 , Xueling Sim  3 , Keven Ang  1 , Tavintharan Subramaniam  4 , Wern Ee Tang  5 , Chee Fang Sum  4 , Jian-Jun Liu  2 , Su Chi Lim  1
Affiliations

Association of leukocyte telomere length with chronic kidney disease in East Asians with type 2 diabetes: a Mendelian randomization study

Resham L Gurung et al. Clin Kidney J. .

Abstract

Background: 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.

Methods: The cross-sectional association of 16 LTL SNPs with CKD, defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2, 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.

Results: 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, Phet = 0.547). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (β = 0.010, P = 0.751).

Conclusions: 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.

Keywords: Mendelian randomization analysis; chronic kidney disease; telomere length; type 2 diabetes.

PubMed Disclaimer

Figures

FIGURE 1:
FIGURE 1:
Scatter plot to visualize the causal effect of LTL on CKD.
FIGURE 2:
FIGURE 2:
Radial plot to visualize individual outlier SNPs in the MR estimates for CKD. Black dots show valid SNPs and green dots (if any) display invalid outlier SNPs. The curved black line represents ratio estimates of each SNPs.
See this image and copyright information in PMC

References

    1. Blackburn EH. Structure and function of telomeres. Nature 1991; 350: 569–573 - PubMed
    1. Melk A, Ramassar V, Helms LMet al. Telomere shortening in kidneys with age. J Am Soc Nephrol 2000; 11: 444–453 - PubMed
    1. Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37: 614–636 - PubMed
    1. Harley CB, Futcher AB, Greider CW.. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345: 458–460 - PubMed
    1. Jylhava J, Pedersen NL, Hagg S.. Biological age predictors. EBioMedicine 2017; 21: 29–36 - PMC - PubMed