Telomeric G-Tail Length and Hospitalization for Cardiovascular Events in Hemodialysis Patients

Abstract

Background and objectives Telomeric G-tails play a pivotal role in maintaining the intramolecular loop structure of telomeres. Previous in vitro studies have suggested that the erosion of telomeric G-tails triggers cellular senescence, leading to organ dysfunction and atherosclerosis. The authors recently established a method to measure telomeric G-tail length using a hybridization protection assay. Using this method, this study investigated whether telomeric G-tail length could be used as a novel predictor for future cardiovascular events in hemodialysis patients.Design, setting, participants, & measurements A prospective observational study was performed involving a cohort of 203 Japanese hemodialysis patients to examine the lengths of telomeric G-tails and total telomeres and subsequent cardiovascular events during a median follow-up period of 48 months. The lengths of telomeric G-tails and total telomeres were also measured in 203 participants who did not have CKD and who were age-and sex-matched to hemodialysis patients. ResultsThe lengths of telomeric G-tails and total telomeres were significantly shorter in hemodialysis patients than in control subjects. Telomeric G-tails, but not total telomeres, were independently and negatively associated with clinical history of cardiovascular disease. During follow-up, 80 cardiovascular events occurred. Total telomere length did not predict cardiovascular events. However, the length of telomeric G-tails was associated with new-onset cardiovascular events (hazard ratio per log luminescence signals, 0.12; 95% confidence interval, 0.12 to 0.50) that persisted after adjustment for age, sex, diabetes mellitus, clinical history of cardiovascular disease, inflammation, use of vitamin D, and serum levels of phosphate and intact parathyroid hormone.Conclusions Longer telomeric G-tail length is associated with a lower risk of future cardiovascular events in hemodialysis patients.

Telomere G-tail Length is a Promising Biomarker Related to White Matter Lesions and Endothelial Dysfunction in Patients With Cardiovascular Risk: A Cross-sectional Study

“…This different distribution might indicate that telomere G-tail length is more strongly influenced by cardiovascular risk factors than is total telomere length. Recently, Hirashio et al reported that shorter telomere G-tail length was associated with future cardiovascular risk in hemodialysis patients, but that total telomere length did not predict cardiovascular events ( Hirashio et al, 2014 ). In addition, our study demonstrated that telomere G-tail length is significantly correlated with endothelial function and the severity of ARWMCs after adjustment for age, sex and baseline characteristics, although the association between total telomere length and these factors was not significant.…”

“…To solve this issue, we previously developed a telomere G-tail HPA method ( Tahara et al, 2005 ) which has the advantages of simple use, accuracy, and high sensitivity for G-tails in vitro. Additionally, recently we developed high-throughput automated machine for G-tail telomere HPA that is applicable for clinical use ( Hirashio et al, 2014 ). Telomere G-tail HPA methods might therefore be more suitable for clinical use than other G-tail length assays.…”

“…However, the association of telomere G-tail length with various cardiovascular risk factors in humans has not been clarified. To our knowledge, only one report has shown an association between the telomere G-tail and cardiovascular events in hemodialysis patients ( Hirashio et al, 2014 ).…”

Telomere Attrition and Elongation after Chronic Dialysis Initiation in Patients with End-Stage Renal Disease

“…Chronic inflammation is common in uremic patients, and we recently demonstrated that reduced TL is associated with inflammatory markers in uremic Caucasian hemodialysis (HD) patients [13] . Moreover, it was reported that a longer telomeric G-tail, that may be important to keep telomere function, was associated with a decreased risk of CVD in Japanese HD patients [14] . The mechanisms whereby these adverse conditions affect telomere biology are unknown and are yet to be determined.…”

Predicting Risk at the End of the End: Telomere G-tail as a Biomarker

“…In other words, G-tail length could fluctuate upon exposure to various stresses. Indeed, G-tail is also shortened in hemodialysis patients ( Hirashio et al, 2014 ). Mechanistically, factors that could modulate G-tail length include telomerase-mediated G-strand extension, end resection of the antisense C-strand, formation and resolution of higher-order structure called G-quadruplexes, loading of the shelterin protein complexes and innate hypersensitivity to oxidative stress.…”