Telomere length correlates with disease severity and inflammation in sickle cell disease.

Background: Telomeres, the ends of linear chromosomes, shorten during mitotic cell division and erosion may be aggravated by inflammation or proliferative and oxidative stress. As the bone marrow is under hyperproliferative pressure in sickle cell disease and several tissues are submitted to chronic inflammation, this study sought to determine the telomere length of patients with sickle cell disease.

Methods: The mean telomere length was measured in peripheral blood leukocytes by quantitative polymerase chain reaction. The age-adjusted telomere to single copy gene ratio was compared between 91 adult sickle cell disease patients and 188 controls.

Results: Sickle cell disease patients had significantly shorter telomeres than the controls (p-value<0.0001). Moreover, among sickle cell disease genotypes, Hb SS patients had significantly shorter telomeres compared to Hb SC and Hb Sβ patients (p-value<0.0001). Patients on hydroxyurea also had shorter telomeres in comparison to those off the drug (p-value=0.02). A positive correlation was observed between telomere length and hemoglobin level (r=0.3; p-value=0.004), whereas negative correlations were detected between telomere length and lymphocyte count (r=-0.3; p-value=0.005) and interleukin-8 serum levels (r=-0.4; p-value=0.02).

Conclusions: The findings of this study indicate that telomeres are short in sickle cell disease patients and that telomere erosion directly correlates with disease genotype, inflammation markers, and the use of hydroxyurea.