Colella Marina Pereira, Santana Barbara A, Conran Nicola, Tomazini Vinicius, Costa Fernando F, Calado Rodrigo T, Saad Sara T Olalla
Universidade Estadual de Campinas/Hemocentro (UNICAMP), Campinas, SP, Brazil.
Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Ribeirão Preto, São Paulo, SP, Brazil.
Rev Bras Hematol Hemoter. 2017 Apr-Jun;39(2):140-145. doi: 10.1016/j.bjhh.2017.02.007. Epub 2017 Mar 11.
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.
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.
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).
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.
端粒是线性染色体的末端，在有丝分裂细胞分裂过程中会缩短，炎症、增殖和氧化应激可能会加剧这种缩短。由于镰状细胞病患者的骨髓处于增殖压力之下，且多个组织存在慢性炎症，本研究旨在确定镰状细胞病患者的端粒长度。
采用定量聚合酶链反应测量外周血白细胞中的平均端粒长度。比较了91例成年镰状细胞病患者和188例对照者经年龄调整后的端粒与单拷贝基因比率。
镰状细胞病患者的端粒明显短于对照组（p值<0.0001）。此外，在镰状细胞病基因型中，与Hb SC和Hb Sβ患者相比，Hb SS患者的端粒明显更短（p值<0.0001）。服用羟基脲的患者与未服用该药物的患者相比，端粒也更短（p值=0.02）。观察到端粒长度与血红蛋白水平呈正相关（r=0.3；p值=0.004），而端粒长度与淋巴细胞计数（r=-0.3；p值=0.005）和白细胞介素-8血清水平（r=-0.4；p值=0.02）呈负相关。
本研究结果表明，镰状细胞病患者的端粒较短，端粒缩短与疾病基因型、炎症标志物以及羟基脲的使用直接相关。
