Age-adjusted telomere Napabucasin price length for each subject was computed by subtracting the subject’s “predicted telomere

length” from his/her observed telomere length. The differences in telomere length between the two groups were evaluated using Student’s t test. A P-value <0.05 was considered statistically significant. From May 2008 to April 2009, 149 patients with hepatic cirrhosis were enrolled in the study. Thirteen patients did not donate buccal mucosa and/or peripheral blood for DNA extraction; one patient withdrew from the study; and the DNA sample from one patient was not adequate for amplification. Thus, samples from 134 patients were available for analysis; their characteristics are described in Table 1. In 67 patients (50%) the diagnosis of cirrhosis was established by liver biopsy; in the remaining patients cirrhosis was diagnosed based on clinical parameters for cirrhosis and portal hypertension. Among the 134 patients with cirrhosis, one heterozygous mutation in TERC was found in one patient and four missense gene variants in TERT were identified in nine patients AZD4547 supplier (cumulative carrier frequency for TERT missense variants, 7%). Eight patients were heterozygous and one was homozygous for the TERT codon

Ala1062Thr gene variant (Tables 2, 3). A 54-year-old female patient with hepatitis C virus-associated cirrhosis was heterozygous for the TERC n.37AG mutation, which has been previously described in one patient with dyskeratosis congenita31 and in one patient with idiopathic pulmonary fibrosis,13 but not in healthy individuals in our study or in other series.32–34 A 56-year-old male patient with alcoholic cirrhosis was heterozygous for a codon 441Glu deletion in the N-terminal region of TERT (Fig. 1A), previously described in aplastic anemia,11 acute myeloid leukemia (in homozygosity),14 and in one healthy subject.11

Two individuals carried novel TERT mutations: a 62-year-old woman with nonalcoholic steatohepatitis (NASH) who was heterozygous for a TERT codon Pro530Leu located in the N-terminal region, and a 48-year-old woman with alcoholic cirrhosis, heterozygous for a TERT codon Thr882Ile in the Reverse Transcriptase Motif D (Fig. 1A). These novel mutations were not found in 528 control subjects. Five patients were heterozygous and one was homozygous for PAK6 the TERT codon Ala1062Thr, located in the C-terminal region and adjacent to Motif E-III (Fig. 1A). The primary etiology for cirrhosis for these patients was chronic hepatitis C virus infection in three; alcoholic cirrhosis in one; primary biliary cirrhosis in one (homozygous); and Wilson’s disease in another. The TERT codon Ala1062Thr gene variant has been previously described in aplastic anemia,11 acute myeloid leukemia,14 idiopathic pulmonary fibrosis,12 and healthy individuals.11 As the TERT codon Ala1062Thr gene variant was observed in low frequency in the 528 control subjects (allele frequency, 0.