Reaching critically short telomeres induces cellular senescence and ultimately cell death. Cellular senescence contributes to the loss of tissue function. We aimed to determine the association between variants within genes involved in telomere length maintenance, posttransplant events, and aortic telomere length in heart transplant patients. DNA was isolated from paired aortic samples of 383 heart recipients (age 50.7 ± 11.9 years) and corresponding donors (age 38.7 ± 12.0 years). Variants within the TERC (rs12696304), TERF2IP (rs3784929 and rs8053257), and OBCF1 (rs4387287) genes were genotyped, and telomere length was measured using qPCR. We identified similar frequencies of genotypes in heart donors and recipients. Antibody-mediated rejection (AMR) was more common (p < 0.05) in carriers of at least one G allele within the TERF2IP locus (rs3784929). Chronic graft dysfunction (CGD) was associated with the TERC (rs12696304) GG donor genotype (p = 0.05). The genetic risk score did not determine posttransplant complication risk prediction. No associations between the analyzed polymorphisms and telomere length were detected in either donor or recipient DNA. In conclusion, possible associations between donor TERF2IP (rs3784929) and AMR and between TERC (rs12696304) and CGD were found. SNPs within the examined genes were not associated with telomere length in transplanted patients.

• Keywords
• SNP, genetic risk score, heart transplantation, rejection, telomere,
• MeSH
• DNA metabolism   MeSH
• Adult MeSH
• Genetic Loci MeSH
• Leukocytes metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Telomere * genetics   MeSH
• Heart Transplantation * adverse effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA MeSH

Despite the rapid progress in diagnosis and treatment of cardiovascular disease (CVD), this disease remains a major cause of mortality and morbidity. Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association studies, has helped to identify new genes and their variants, which can be used for calculations of risk, prediction of treatment efficacy, or detection of subjects prone to drug side effects. Although the use of genetic risk scores further improves CVD prediction, the significance is not unambiguous, and some subjects at risk remain undetected. Further research directions should focus on the "second level" of genetic information, namely, regulatory molecules (miRNAs) and epigenetic changes, predominantly DNA methylation and gene-environment interactions.

• Keywords
• cardiovascular disease, epigenetic, gene, gene score, interaction, polymorphism,
• MeSH
• Genome-Wide Association Study methods   MeSH
• Genetic Predisposition to Disease MeSH
• Genetic Testing methods   MeSH
• Precision Medicine methods   MeSH
• Cardiovascular Diseases diagnosis   genetics   therapy   MeSH
• Humans MeSH
• Nutrigenomics methods   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The aim of this study was to ascertain whether long-term occupational exposure to nanoparticles would affect relative leukocyte telomere length (LrTL). We analysed occupational exposure to size-resolved aerosol particles, with special emphasis on nanoparticles at two workshops: i/ the production of nanocomposites containing metal oxides; ii/ laboratory to test experimental exposure of nano-CuO to rodents. Thirty five exposed researchers (age 39.5 ± 12.6 yr; exposure duration 6.0 ± 3.7 yr) and 43 controls (40.4 ± 10.5 yr) were examined. LrTL did not significantly (p=0.14) differ between the exposed researchers (0.92 ± 0.13) and controls (0.86 ± 0.15). In addition, no significant correlation (r=-0.22, p=0.22) was detected between the duration of occupational exposure and LrTL. The results remained non-significant after multiple adjustments for age, sex and smoking status. Our pilot results suggest that relative leukocyte telomere length is not affected by occupational exposure to nanoparticles.

• Keywords
• Follow-up, Metal nanoparticles, Telomere length,
• MeSH
• Adult MeSH
• Metal Nanoparticles adverse effects   MeSH
• Air Pollutants, Occupational adverse effects   MeSH
• Leukocytes MeSH
• Middle Aged MeSH
• Humans MeSH
• Oxides MeSH
• Occupational Exposure adverse effects   MeSH
• Research Personnel * MeSH
• Telomere Shortening drug effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Air Pollutants, Occupational MeSH
• Oxides MeSH

BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

• Keywords
• Genetic variants, Mendelian randomization, Renal cell carcinoma, Risk, Telomere length,
• MeSH
• Genome-Wide Association Study MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Risk Assessment MeSH
• Telomere Homeostasis * MeSH
• Polymorphism, Single Nucleotide * MeSH
• Carcinoma, Renal Cell blood   genetics   pathology   MeSH
• Leukocytes chemistry   MeSH
• Humans MeSH
• Mendelian Randomization Analysis MeSH
• Kidney Neoplasms blood   genetics   pathology   MeSH
• Odds Ratio MeSH
• Risk Factors MeSH
• Case-Control Studies MeSH
• Telomere genetics   pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH