Relative Telomere Length and Stroke Risk in a Chinese Han Population

Gao, Dan; Zhang, Rui; Ji, Guofa; Li, Chunqi; Guo, Dangshe; Jin, Tianbo; Chen, Mingwei

doi:10.1007/s12031-018-1160-9

Cited by 11 publications

(6 citation statements)

References 28 publications

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“…Conventional observational studies have shown inconclusive associations of telomere shortening and the risk of stroke. Consistently, several original studies reported positive association between telomere shortening and the risk of stroke [ 12 – 14 ]. In contrast, evidence also suggests that shorter telomeres were not significantly associated with stroke risk [ 15 – 17 ].…”

Section: Introductionsupporting

confidence: 72%

Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese population: a linear and non-linear Mendelian randomization analysis

et al. 2020

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Background Many contradictory conclusions pertaining to the telomere length in peripheral leukocyte chromosomes as a potential biomarker for ischemic stroke (IS) risk have been reported by the various observational studies in previous years. This study aims to investigate whether the leukocyte telomere length is associated with an increased IS risk or not, based on the Mendelian randomization (MR) approach. Methods Based on the NHGRI-EBI GWAS Catalog database, the Chinese online genetic database as well as the previous published studies, twelve single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 0.05 were selected and the leukocyte telomere length was measured in 431 first-ever IS patients and 304 healthy controls (quantitative polymerase chain reaction). To explore linear and non-linear effect of telomere length on the IS risk, we preformed the linear MR analysis (the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method), and the non-linear MR analysis (semiparametric method with three tests for non-linearity, including the quadratic test, Cochran’s Q test, and the fractional polynomial test). Results Two verified SNPs (rs11125529 and rs412658) were chosen as instrumental variables. In linear MR analysis, the adjusted odds ratios and 95% confidence intervals of IS for genetically predicted telomere lengths, based on the two SNPs, were 1.312 (0.979 to 1.759), 1.326 (0.932 to 1.888) and 1.226 (0.844 to 1.781) for the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method, respectively. Three tests for nonlinearity failed to reject the null exactly, indicating that the relationship between telomere length and IS risk is unlikely to be non-linear. Conclusion This MR study based on individual data does not provide strong evidence for a positive linear or non-linear effect of telomere length on the IS risk.

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Section: Introductionsupporting

confidence: 72%

Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese population: a linear and non-linear Mendelian randomization analysis

et al. 2020

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“…Among Caucasians, no such link between TERT gene polymorphisms and IS risk has been observed [15]. In the population-based GWAS study by Wei et al [16] the TERT rs2736100 SNP was reportedly signi cantly associated with LTL, while another report indicated that the TERT C and G alleles of the rs2853691 and rs33954691 genotypes were associated with shorter LTL [17]. When studying TERT polymorphisms in the Chinese population, Zhang et al[6] found that the TERT rs224652 G/A (superdominant model) and A/A (dominant model) genotypes were associated with elevated IS risk.…”

Section: Discussionmentioning

confidence: 99%

Association and causal impact of TERT genetic variants on peripheral blood leukocyte telomere length and cerebral small vessel disease risk in a Chinese Han population: a Mendelian randomization analysis

Shi

Geng

et al. 2023

Preprint

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Background Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD. Methods Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk. Results Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk. Conclusion Multiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk.

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“…This observation alludes to additional telomere-related effects in CVD that go beyond normal age-related telomere shortening. In addition to coronary atherosclerosis and myocardial ischemia, the risk of ischemic, atherothrombotic, and haemorrhagic stroke also seems to be associated with telomere length [89][90][91][92][93]. Also, Martin-Ruiz et al found that telomere length is associated with post-stroke mortality [94].…”

Section: Cardiovascular Diseases (Cvd)mentioning

confidence: 99%

Telomeres and Age-Related Diseases

et al. 2021

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Telomeres are at the non-coding ends of linear chromosomes. Through a complex 3-dimensional structure, they protect the coding DNA and ensure appropriate separation of chromosomes. Aging is characterized by a progressive shortening of telomeres, which compromises their structure and function. Because of their protective function for genomic DNA, telomeres appear to play an important role in the development and progression of many age-related diseases, such as cardiovascular disease (CVD), malignancies, dementia, and osteoporosis. Despite substantial evidence that links telomere length with these conditions, the nature of these observations remains insufficiently understood. Therefore, future studies should address the question of causality. Furthermore, analytical methods should be further improved with the aim to provide informative and comparable results. This review summarize the actual knowledge of telomere biology and the possible implications of telomere dysfunction for the development and progression of age-related diseases. Furthermore, we provide an overview of analytical techniques for the measurement of telomere length and telomerase activity.

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Relative Telomere Length and Stroke Risk in a Chinese Han Population

Cited by 11 publications

References 28 publications

Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese population: a linear and non-linear Mendelian randomization analysis

Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese population: a linear and non-linear Mendelian randomization analysis

Association and causal impact of TERT genetic variants on peripheral blood leukocyte telomere length and cerebral small vessel disease risk in a Chinese Han population: a Mendelian randomization analysis

Telomeres and Age-Related Diseases

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