Abstract | RATIONALE: OBJECTIVES: To test whether telomere shortening is a frequent mechanism underlying pulmonary fibrosis, we have characterized telomere lengths in subjects with familial or sporadic disease who do not have coding mutations in TERT or TERC. METHODS: Using a modified Southern blot assay, the telomerase restriction fragment length method, and a quantitative polymerase chain reaction assay we have measured telomere lengths of genomic DNA isolated from circulating leukocytes from normal control subjects and subjects with pulmonary fibrosis. MEASUREMENTS AND MAIN RESULTS: All affected patients with telomerase mutations, including case subjects heterozygous for newly reported mutations in TERT, have short telomere lengths. A significantly higher proportion of probands with familial pulmonary fibrosis (24%) and sporadic case subjects (23%) in which no coding mutation in TERT or TERC was found had telomere lengths less than the 10th percentile when compared with control subjects (P = 2.6 x 10(-8)). Pulmonary fibrosis affectation status was significantly associated with telomerase restriction fragment lengths, even after controlling for age, sex, and ethnicity (P = 6.1 x 10(-11)). Overall, 25% of sporadic cases and 37% of familial cases of pulmonary fibrosis had telomere lengths less than the 10th percentile. CONCLUSIONS: A significant fraction of individuals with pulmonary fibrosis have short telomere lengths that cannot be explained by coding mutations in telomerase. Telomere shortening of circulating leukocytes may be a marker for an increased predisposition toward the development of this age-associated disease.
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Authors | Jennifer T Cronkhite, Chao Xing, Ganesh Raghu, Kelly M Chin, Fernando Torres, Randall L Rosenblatt, Christine Kim Garcia |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 178
Issue 7
Pg. 729-37
(Oct 01 2008)
ISSN: 1535-4970 [Electronic] United States |
PMID | 18635888
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- telomerase RNA
- RNA
- TERT protein, human
- Telomerase
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Case-Control Studies
- Female
- Genetic Predisposition to Disease
(genetics)
- Humans
- Male
- Middle Aged
- Mutation, Missense
- Pedigree
- Pulmonary Fibrosis
(genetics)
- RNA
(genetics)
- Regeneration
(genetics)
- Telomerase
(genetics)
- Telomere
(pathology)
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