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Short Telomere Lengthand Ischemic HeartDisease:Observational andGenetic Studies in290 022 Individuals Alexander Scheller MadridLine RodeBørge G. Nordestgaard2016 год

Short Telomere Length and Ischemic Heart Disease: Observational and Genetic Studies in 290 022 Individuals
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Аннотация: Abstract BACKGROUND Short telomeres are associated with aging and have been associated with a high risk of ischemic heart disease in observational studies; however, the latter association could be due to residual confounding and/or reverse causation. We wanted to test the hypothesis that short telomeres are associated with high risk of ischemic heart disease using a Mendelian randomization approach free of reverse causation and of most confounding. METHODS We genotyped 3 genetic variants in OBFC1 (oligonucleotide/oligosaccharide binding fold containing 1), TERT (telomerase reverse transcriptase), and TERC (telomerase RNA component), which code for proteins and RNA involved in telomere maintenance. We studied 105 055 individuals from Copenhagen; 17 235 of these individuals were diagnosed with ischemic heart disease between 1977 and 2013, and 66 618 had telomere length measured. For genetic studies, we further included the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) consortium dataset, which included up to 184 967 participants and 60 837 cases of ischemic heart disease. We conducted multivariable adjusted Cox proportional hazard models for observational estimates, using logistic and instrumental variable analysis for genetic estimates. RESULTS Observationally, a 200-bp–shorter telomere length was associated with a multivariable adjusted hazard ratio for ischemic heart disease of 1.02 (95% CI, 1.01–1.03). Per allele, telomeres were shorter by 67 bp (73–60). In meta-analyses of all 4 studies combined, odds ratios for ischemic heart disease were 1.05 (1.03–1.08) for OBCF1, 1.04 (1.02–1.06) for TERT, and 1.01 (0.99–1.03) for TERC. A genetically determined 200-bp–shorter telomere length was associated with an odds ratio for ischemic heart disease of 1.10 (1.06–1.14). CONCLUSIONS Shorter telomeres were associated with a higher risk of ischemic heart disease, both observationally and genetically.
Год издания: 2016
Авторы: Alexander Scheller Madrid, Line Rode, Børge G. Nordestgaard, Stig E. Bojesen
Издательство: American Association for Clinical Chemistry
Источник: Clinical Chemistry
Ключевые слова: Telomeres, Telomerase, and Senescence, Genetics, Aging, and Longevity in Model Organisms
Другие ссылки: Clinical Chemistry (PDF)
Clinical Chemistry (HTML)
PubMed (HTML)