{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:57:39Z","timestamp":1791417459319,"version":"4.3.3"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1584,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      <jats:bold>Some patients with liver disease progress to cirrhosis, but the risk factors for cirrhosis development are unknown. Dyskeratosis congenita, an inherited bone marrow failure syndrome associated with mucocutaneous anomalies, pulmonary fibrosis, and cirrhosis, is caused by germline mutations of genes in the telomerase complex. We examined whether telomerase mutations also occurred in sporadic cirrhosis. In all, 134 patients with cirrhosis of common etiologies treated at the Liver Research Institute, University of Arizona, between May 2008 and July 2009, and 528 healthy subjects were screened for variation in the<\/jats:bold>\n                      <jats:bold>TERT<\/jats:bold>\n                      <jats:bold>and<\/jats:bold>\n                      <jats:bold>TERC<\/jats:bold>\n                      <jats:bold>genes by direct sequencing; an additional 1,472 controls were examined for the most common genetic variation observed in patients. Telomere length of leukocytes was measured by quantitative polymerase chain reaction. Functional effects of genetic changes were assessed by transfection of mutation-containing vectors into telomerase-deficient cell lines, and telomerase activity was measured in cell lysates. Nine of the 134 patients with cirrhosis (7%) carried a missense variant in<\/jats:bold>\n                      <jats:bold>TERT<\/jats:bold>\n                      <jats:bold>, resulting in a cumulative carrier frequency significantly higher than in controls (<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.0009). One patient was homozygous and eight were heterozygous. The allele frequency for the most common missense<\/jats:bold>\n                      <jats:bold>TERT<\/jats:bold>\n                      <jats:bold>variant was significantly higher in patients with cirrhosis (2.6%) than in 2,000 controls (0.7%;<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.0011). One additional patient carried a<\/jats:bold>\n                      <jats:bold>TERC<\/jats:bold>\n                      <jats:bold>mutation. The mean telomere length of leukocytes in patients with cirrhosis, including six mutant cases, was shorter than in age-matched controls (<\/jats:bold>\n                      <jats:bold>P<\/jats:bold>\n                      <jats:bold>= 0.0004).<\/jats:bold>\n                      <jats:bold>Conclusion:<\/jats:bold>\n                      <jats:bold>Most<\/jats:bold>\n                      <jats:bold>TERT<\/jats:bold>\n                      <jats:bold>gene variants reduced telomerase enzymatic activity<\/jats:bold>\n                      <jats:bold>in vitro<\/jats:bold>\n                      <jats:bold>. Loss-of-function telomerase gene variants associated with short telomeres are risk factors for sporadic cirrhosis. (Hepatology 2011;)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.24173","type":"journal-article","created":{"date-parts":[[2011,1,12]],"date-time":"2011-01-12T18:52:27Z","timestamp":1294858347000},"page":"1600-1607","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":170,"title":["Constitutional telomerase mutations are genetic risk factors for cirrhosis"],"prefix":"10.1097","volume":"53","author":[{"given":"Rodrigo T.","family":"Calado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Brudno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulomi","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph 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