Abstract
Oxidative stress is involved in the pathogenesis of airway obstruction in α1-antitrypsin deficient patients. This may result in a shortening of telomere length, resulting in cellular senescence. To test whether telomere length differs in α1-antitrypsin deficient patients compared with controls, we measured telomere length in DNA from peripheral blood cells of 217 α1-antitrypsin deficient patients and 217 control COPD patients. We also tested for differences in telomere length between DNA from blood and DNA from lung tissue in a subset of 51 controls. We found that telomere length in the blood was significantly longer in α1-antitrypsin deficient COPD patients compared with control COPD patients (p = 1×10−29). Telomere length was not related to lung function in α1-antitrypsin deficient patients (p = 0.3122) or in COPD controls (p = 0.1430). Although mean telomere length was significantly shorter in the blood when compared with the lungs (p = 0.0078), telomere length was correlated between the two tissue types (p = 0.0122). Our results indicate that telomere length is better preserved in α1-antitrypsin deficient COPD patients than in non-deficient patients. In addition, measurement of telomere length in the blood may be a suitable surrogate for measurement in the lung.
Highlights
Chronic obstructive pulmonary disease (COPD) is a complex trait with both genetic and environmental risks factors that is characterized by non-reversible airway obstruction and chronic inflammation
Patients with a1-antitrypsin deficiency have longer telomere lengths in peripheral leukocytes compared with COPD patients who do not have a1-antitrypsin deficiency
There was no significant relationship between telomere length in blood and lung function as measured by FEV1% predicted in a1-antitrypsin deficient patients or in COPD controls
Summary
Chronic obstructive pulmonary disease (COPD) is a complex trait with both genetic and environmental risks factors that is characterized by non-reversible airway obstruction and chronic inflammation. The search for the genes responsible for this disorder has involved the investigation of candidate genes [9] as well as genome-wide association studies of COPD [10,11] and lung function in the general population [12,13,14,15]. These studies have identified novel genes such as Hedgehog-interacting protein [11,12,13,15,16], anicotinic acetylcholine receptor [11,17] and 5-hydroxytryptamine (serotonin) receptor 4 [12,13,15]. We determined whether the length of telomeres in peripheral blood DNA is correlated with that in lung tissue samples in order to test the hypothesis that COPD is a ‘‘systemic’’ disease, and that telomeric shortening in this condition affects both lung and the hematopoietic systems
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