The association between leukocyte telomere length, telomere attrition and disease severity in cystic fibrosis patients

Background: Cellular senescence(definition) triggered by telomere(definition) shortening contributes to aging. Telomeres shorten during life with shorter leukocyte telomere length (LTL) being a risk factor for age-related diseases. Median survival of CF patients continues to increase. Aim: Investigating the association between LTL and LTL attrition and measures of disease severity in adult and pediatric CF patients. Methods: Peripheral blood from 176 CF patients (age 0-72) was collected and buffy coat DNA was extracted. DNA extracted for genotype analysis (between 1990-2013) of 85 included patients was available. Relative LTL was determined using a real-time qPCR method. For the 85 patients also having a historical sample LTL attrition was defined as the difference in LTL between 2 time-points divided by the number of years in-between. Results: Diagnosis of CF asthma and treatment with inhaled corticosteroids (ICS) was associated with 13.4% shorter LTL (p<0.0001). Each percent decrease in FEV1 was associated with 0.13% shorter LTL after adjusting for age, BMI and gender (p=0.043). The effect of genotype after adjusting for age, BMI, ICS and vitamin D level was gender-specific as only male ΔF508 homozygotes had 9.1% shorter LTL compared with heterozygotes (p=0.032). However, both male and female homozygotes had a 7.3% higher LTL attrition rate compared with heterozygotes (p<0.0001). This effect was age-dependent (p<0.0001) with younger patients having a higher attrition rate. Conclusion: Our results suggest that CF patients suffering from severe disease characterized by lower FEV1, ΔF508 homozygosity and CF asthma have shorter LTL and higher attrition rate, suggestive of increased senescence.