Telomerase gene mutations and telomere length shortening in patients with idiopathic pulmonary fibrosis in a Chinese population

Background and objective: Idiopathic pulmonary fibrosis (IPF) is an age-related disease and the most common manifestation of telomere-mediated disorders.

Methods: We collected detailed medical histories and DNA samples from 100 IPF patients seen at Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University. All patients had sporadic IPF, with no family history reported. We screened all patients for telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) variants, and measured their telomere lengths in lymphocytes.

Results: Six novel telomerase gene mutations were identified in six IPF patients enrolled in the studies. They were two heterozygous mutations in TERC (257 G>A and 108 C>T) and four in TERT (R622H, T644M, V777L and F1032I). IPF patients with TERT/TERC mutations had significant thrombocytopaenia (160.167 ± 28.089 × 10(9)) compared with the non-mutation groups (191.018 ± 71.187 × 10(9), P = 0.047). All IPF patients with TERT/TERC mutations had shortened telomeres (0.656 ± 0.125) compared with the patients lacking TERT/TERC mutations (1.080 ± 0.6819, P = 0.0184). IPF patients lacking TERT or TERC mutations (1.080 ± 0.6819) had significantly shorter telomeres compared with age-matched healthy controls (1.244 ± 0.5890, P = 0.0355).

Conclusions: Six novel mutations in the telomerase genes were identified for the first time in individuals diagnosed with sporadic IPF in a Chinese Han population. Shorter telomeres and mild thrombocytopaenia could be clues to association with telomerase gene mutation and sporadic IPF.