scholarly journals Analysis of the Association Between TERC and TERT Genetic Variation and Leukocyte Telomere Length and Human Lifespan—A Follow-Up Study

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 82 ◽  
Author(s):  
Daniela Scarabino ◽  
Martina Peconi ◽  
Franca Pelliccia ◽  
Rosa Maria Corbo

We investigated the possible influence of TERC and TERT genetic variation and leukocyte telomere length (LTL) on human lifespan. Four polymorphisms of TERT and three polymorphisms of TERC were examined in a sample of elderly subjects (70–100 years). After nine years of follow-up, mortality data were collected, and sub-samples of long-lived/not long-lived were defined. TERT VNTR MNS16A L/L genotype and TERT rs2853691 A/G or G/G genotypes were found to be associated with a significantly higher risk to die before the age of 90 years, and with a significantly lower age at death. The association between lifespan and LTL at baseline was analyzed in a subsample of 163 subjects. Age at baseline was inversely associated with LTL (p < 0.0001). Mean LTL was greater in the subjects still living than in those no longer living at follow-up (0.79 T/S ± 0.09 vs 0.63 T/S ± 0.08, p < 0.0001). Comparison of age classes showed that, among the 70–79-year-olds, the difference in mean LTL between those still living and those no longer living at follow-up was greater than among the 80–90-year-olds. Our data provide evidence that shorter LTL at baseline may predict a shorter lifespan, but the reliability of LTL as a lifespan biomarker seems to be limited to a specific age (70–79 years).

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Caroline Goode ◽  
Jinying Zhao ◽  
Richard B Devereux ◽  
Santosh Murthy ◽  
Alexander E Merkler ◽  
...  

Introduction: Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We hypothesized that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (SHFS). Methods: The SHFS is a population-based cohort study of cardiovascular disease (CVD) and its risk factors. Participants (n=2,769) recruited from regions in Arizona, Oklahoma and the Dakotas were assessed for LTL and CVD risk factors during a clinic visit between 2001 and 2003. Incident stroke events were identified through the end of 2018 (mean follow-up: 16.4 years). We assessed the association between LTL and incident stroke using frailty models based on the proportional hazards, accounting for family relatedness and established stroke risk factors that include sex, geographical location, education, smoking, atrial fibrillation, diabetes mellitus, and hypertension. Results: Among 2,769 participants, the mean age was 40.6±17.2 and 41.4% were male. During follow-up, there were 79 (2.9%) incident stroke cases. In the primary model, which adjusted for demographic variables (sex, location and education), the hazard ratios (HR) for stroke in participants in the first and second LTL quartiles were significantly higher than those in the highest (longest) LTL quartile, with HRs of 3.1 (95%CI: 1.4 - 6.6) and 3.5 (95%CI: 1.7 - 7.5), respectively. After adjusting for smoking, atrial fibrillation, diabetes mellitus, and hypertension, the association between LTL and stroke was attenuated, but remained significant when comparing the second shortest LTL quartile to the longest LTL quartile, HR: 2.3 (95% CI: 1.1 – 5.0). Conclusions: In summary, LTL was associated with incident stroke among SHFS participants. Those with shorter LTL have higher risk of stroke. Longer follow-up time may add more power to data analyses since the SHFS is relatively young, with an average baseline age of 40 years. If results are confirmed in other populations, LTL may serve as a biomarker identifying high risk individuals for the purpose of stroke prevention.


2015 ◽  
Vol 22 (6) ◽  
pp. 637-644 ◽  
Author(s):  
Taiki Yukutake ◽  
Minoru Yamada ◽  
Naoto Fukutani ◽  
Shu Nishiguchi ◽  
Hiroki Kayama ◽  
...  

2001 ◽  
Vol 11 (3) ◽  
pp. 245-251 ◽  
Author(s):  
P.M. Puska ◽  
A.H.A. Tarkkanen

Purpose To examine changes in visual acuity (VA) and refraction in non-glaucomatous patients with unilateral exfoliation syndrome (EXS). Methods The best corrected values for VA (Snellen acuity cards) subjectively adjusted for refraction, and IOP were measured, and the development of lens opacities was examined in 46 non-glaucomatous patients with unilateral EXS. Results After five years the rate of conversion to bilateral exfoliation was 22% and to exfoliative glaucoma 30%. There was a significant decrease in VA in the exfoliative (E) eyes (median; QI, QIII, range: 1; 0.8, 1, 0.4-1.3 vs. 0.55; 0.4, 1, 0.05-1.4, p<0.0001) and the fellow, initially non-exfoliative (NE), eyes (1; 0.9, 1, 0.3–1.3 vs. 0.7; 0.5, 0.9, 0.1–1.4, p<0.0001) and a significant myopic change in refraction in the E eyes (+1.02 ± 2.48 vs. +0.11 ± 3.06, p=0.0001) and the NE eyes (+0.99 ± 2.25 vs. +0.43 ± 2.55 D, p<0.01). At study entry the difference in refraction between the fellow eyes (refraction in the NE eye – refraction in the E eye) was −0.27 ± 1.00D. After five years it was +0.32 ± 1.44 (p 0.016), reflecting greater myopic changes in the E eyes. The main type of lens opacification was nuclear sclerosis. Conclusions In five years, significant decreases in VA and myopic shifts in refraction occurred in the E and fellow eyes. The E eyes showed significantly greater myopic changes than the fellow eyes; the cause was clearly nuclear sclerosis, which must be taken into account in the long-term management of patients with EXS.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 580-580 ◽  
Author(s):  
Xavier Pivot ◽  
Mark D. Pegram ◽  
Javier Cortes ◽  
Diana Lüftner ◽  
Gary H. Lyman ◽  
...  

580 Background: SB3 is an approved biosimilar of reference trastuzumab (TRZ). At additional 2-year follow-up after completing neoadjuvant and adjuvant treatment, there was a difference in event-free survival (EFS), but no difference in overall survival (OS) between SB3 and TRZ. Upon monitoring quality attributes of TRZ, a marked downward shift in antibody-dependent cell-mediated cytotoxicity activities (ADCC) was observed in TRZ lots with expiry dates from Aug 2018 to Dec 2019. Some of the lots were used in the Phase III study. This is a post-hoc analysis of EFS and OS by ADCC status from a 3-year follow-up to investigate the difference in EFS between SB3 and TRZ. Methods: After completion of neoadjuvant and adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study (NCT02771795). Within the TRZ group, patients exposed to at least one shifted ADCC lot and those never exposed to shifted ADCC lot during neoadjuvant period were considered as “Exposed” and “Unexposed,” respectively. EFS and OS after 3-year follow-up was analyzed by ADCC status in the long-term follow-up set. Results: 367 patients (SB3, N = 186; TRZ, N = 181) were enrolled in the follow-up study. Within TRZ, 55 patients were Unexposed and 126 patients were Exposed. At a median follow-up duration of 40.8 months in SB3 and 40.5 months in TRZ, 3-year EFS rates were 92.5% in SB3, 94.5% in Unexposed, and 82.5% in Exposed and OS rates were 97.0%, 100%, and 90.6%, respectively. Exposed was associated with decreased EFS compared to Unexposed (HR 0.14, 95% CI 0.04-0.51, p= 0.003). There was a trend of decreased OS in Exposed compared to Unexposed, however, there was no significant difference (HR 0.14, 95% CI 0.02-1.15, p= 0.068). Between SB3 and Unexposed, no difference was observed in EFS (HR 1.06, 95% CI 0.33-3.44, p= 0.923), or OS (HR 0.54, 95% CI 0.05-5.44, p= 0.600). Conclusions: Within the TRZ group, Exposed showed significantly lower EFS compared to Unexposed, and a similar trend was observed in OS with no statistical significance. Between SB3 and Unexposed, no significant difference in EFS or OS was observed. Clinical trial information: NCT02771795.


2015 ◽  
Vol 7 (2) ◽  
pp. 144
Author(s):  
Simon Toupance ◽  
Ghassan Watfa ◽  
Cécile Lakomy ◽  
Anna Kearney-Schwartz ◽  
Carlos Labat ◽  
...  

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