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Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation

Telomeres are repetitive DNA sequences that protect the ends of linear chromosomes, and they are maintained by a ribonucleoprotein complex called telomerase. Variants in genes encoding for telomerase components have been associated with a spectrum of disease in the lung, skin, bone marrow, and liver...

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Autores principales: Chiu, Victor, Hogen, Rachel, Sher, Linda, Wadé, Niquelle, Conti, David, Martynova, Anastasia, Li, Hongtao, Liang, Gangning, O'Connell, Casey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594079/
https://www.ncbi.nlm.nih.gov/pubmed/30964210
http://dx.doi.org/10.1002/hep.30557
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author Chiu, Victor
Hogen, Rachel
Sher, Linda
Wadé, Niquelle
Conti, David
Martynova, Anastasia
Li, Hongtao
Liang, Gangning
O'Connell, Casey
author_facet Chiu, Victor
Hogen, Rachel
Sher, Linda
Wadé, Niquelle
Conti, David
Martynova, Anastasia
Li, Hongtao
Liang, Gangning
O'Connell, Casey
author_sort Chiu, Victor
collection PubMed
description Telomeres are repetitive DNA sequences that protect the ends of linear chromosomes, and they are maintained by a ribonucleoprotein complex called telomerase. Variants in genes encoding for telomerase components have been associated with a spectrum of disease in the lung, skin, bone marrow, and liver. Mutations in the telomerase reverse transcriptase and telomerase RNA component genes have been observed at a higher prevalence in patients with liver disease compared with the general population; however, the presence of variants in other components of the telomerase complex and their impact on clinical outcomes has not been explored. We evaluated 86 patients with end‐stage liver disease for variants in an expanded panel of eight genes, and found that 17 patients (20%) had likely deleterious variants by in silico analysis. Seven unique likely deleterious variants were identified in the regulator of telomere elongation helicase 1 (RTEL1) gene that encodes for a DNA helicase important in telomere maintenance and genomic stability. In gene burden association analysis of their clinical data, the presence of any RTEL1 variant was associated with a 29% lower baseline white blood cell count (95% confidence interval [CI], ‐7% to ‐46%; P Value = 0.01) compared with patients without RTEL1 variants, and the presence of any exonic missense RTEL1 variant was associated with a 42% lower baseline platelet count (95% CI, ‐5% to ‐65%: P Value = 0.03). The presence of any telomerase variant was associated with an increased number of readmissions within 1 year after transplantation demonstrated by an incident rate ratio (IRR) of 3.15 (95% CI, 1.22 to 8.57). No association with survival was observed. Conclusion: Among patients who underwent liver transplantation, the presence of any exonic missense variant was associated with a longer postoperative length of stay with an IRR of 2.16 (95% CI, 1.31 to 3.68).
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spelling pubmed-65940792019-07-10 Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation Chiu, Victor Hogen, Rachel Sher, Linda Wadé, Niquelle Conti, David Martynova, Anastasia Li, Hongtao Liang, Gangning O'Connell, Casey Hepatology Original Articles Telomeres are repetitive DNA sequences that protect the ends of linear chromosomes, and they are maintained by a ribonucleoprotein complex called telomerase. Variants in genes encoding for telomerase components have been associated with a spectrum of disease in the lung, skin, bone marrow, and liver. Mutations in the telomerase reverse transcriptase and telomerase RNA component genes have been observed at a higher prevalence in patients with liver disease compared with the general population; however, the presence of variants in other components of the telomerase complex and their impact on clinical outcomes has not been explored. We evaluated 86 patients with end‐stage liver disease for variants in an expanded panel of eight genes, and found that 17 patients (20%) had likely deleterious variants by in silico analysis. Seven unique likely deleterious variants were identified in the regulator of telomere elongation helicase 1 (RTEL1) gene that encodes for a DNA helicase important in telomere maintenance and genomic stability. In gene burden association analysis of their clinical data, the presence of any RTEL1 variant was associated with a 29% lower baseline white blood cell count (95% confidence interval [CI], ‐7% to ‐46%; P Value = 0.01) compared with patients without RTEL1 variants, and the presence of any exonic missense RTEL1 variant was associated with a 42% lower baseline platelet count (95% CI, ‐5% to ‐65%: P Value = 0.03). The presence of any telomerase variant was associated with an increased number of readmissions within 1 year after transplantation demonstrated by an incident rate ratio (IRR) of 3.15 (95% CI, 1.22 to 8.57). No association with survival was observed. Conclusion: Among patients who underwent liver transplantation, the presence of any exonic missense variant was associated with a longer postoperative length of stay with an IRR of 2.16 (95% CI, 1.31 to 3.68). John Wiley and Sons Inc. 2019-04-09 2019-06 /pmc/articles/PMC6594079/ /pubmed/30964210 http://dx.doi.org/10.1002/hep.30557 Text en © 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Chiu, Victor
Hogen, Rachel
Sher, Linda
Wadé, Niquelle
Conti, David
Martynova, Anastasia
Li, Hongtao
Liang, Gangning
O'Connell, Casey
Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation
title Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation
title_full Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation
title_fullStr Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation
title_full_unstemmed Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation
title_short Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation
title_sort telomerase variants in patients with cirrhosis awaiting liver transplantation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594079/
https://www.ncbi.nlm.nih.gov/pubmed/30964210
http://dx.doi.org/10.1002/hep.30557
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