Levstek Tina, Breznik Nika, Vujkovac Bojan, Nowak Albina, Trebušak Podkrajšek Katarina
Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
Biomedicines. 2024 Aug 1;12(8):0. doi: 10.3390/biomedicines12081724.
Fabry disease (FD) leads to significant morbidity and mortality, which may indicate accelerated ageing. However, it is still unclear whether there is a relationship between telomere length (TL), a marker of biological ageing, and disease outcome. We aimed to examine the relationship between leukocyte TL (LTL) dynamics and the presence of advanced disease stages and/or late complications of FD, including hypertrophic cardiomyopathy, nephropathy and stroke, both cross-sectionally and longitudinally. DNA was extracted from peripheral blood leukocytes and quantitative PCR was utilized to determine relative LTL in 99 Fabry patients. In the longitudinal analysis, we included 50 patients in whom at least three measurements were performed over a period of 5-10 years. The results showed a significant inverse correlation between LTL and age (ρ = -0.20, = 0.05). No significant differences in LTL were found between females and males ( = 0.79) or between patients receiving disease-specific therapy and those without ( = 0.34). In a cross-sectional analysis, no association was found between the presence ( = 0.15) or number ( = 0.28) of advanced stages of the disease and/or late complications and LTL. Similarly, in a longitudinal analysis, no difference in LTL dynamics was found regarding the presence ( = 0.16) of advanced stage organ involvement and/or late complications or their number. These findings indicate that LTL dynamics in adulthood may not be a reliable indicator of disease outcomes in Fabry patients. Therefore, LTL may more accurately reflect the disease burden in early life, when TL is primarily determined.
法布里病（FD）会导致严重的发病和死亡，这可能预示着衰老加速。然而，作为生物衰老标志物的端粒长度（TL）与疾病预后之间是否存在关联仍不清楚。我们旨在通过横断面和纵向研究，探讨白细胞端粒长度（LTL）动态变化与FD晚期疾病阶段和/或晚期并发症（包括肥厚性心肌病、肾病和中风）的存在之间的关系。从外周血白细胞中提取DNA，并利用定量PCR测定99例法布里病患者的相对LTL。在纵向分析中，我们纳入了50例在5至10年期间至少进行了三次测量的患者。结果显示，LTL与年龄之间存在显著的负相关（ρ = -0.20，P = 0.05）。在女性和男性之间（P = 0.79）或接受疾病特异性治疗的患者与未接受治疗的患者之间（P = 0.34），未发现LTL有显著差异。在横断面分析中，未发现疾病晚期阶段和/或晚期并发症的存在（P = 0.15）或数量（P = 0.28）与LTL之间存在关联。同样，在纵向分析中，未发现晚期器官受累和/或晚期并发症的存在（P = 0.16）或数量对LTL动态变化有影响。这些发现表明，成年期的LTL动态变化可能不是法布里病患者疾病预后的可靠指标。因此，LTL可能更准确地反映生命早期的疾病负担，因为此时TL主要是确定的。
