Telomere length is shorter in healthy offspring of subjects with coronary artery disease: support for the telomere hypothesis
Telomere length is shorter in healthy offspring of subjects with coronary artery disease: support for the telomere hypothesis
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DOI：
10.1136/hrt.2007.139675
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发表时间：
2008-04-01
期刊：
影响因子：
5.7
通讯作者：
Samani, N. J.
中科院分区：
文献类型：
--
作者：
Brouilette, S. W.;Whittaker, A.;Samani, N. J.
背景：冠状动脉疾病（CAD）受试者的端粒较短，可能表明过早的生物老化。然而，较短的端粒是否是原发性异常或继发于疾病尚不清楚。目的：为了调查较短的端粒是否是原发性异常或继发于CAD，比较健康年轻人与CAD家族风险的端粒长度。设计：病例对照研究。方法：采用Southern印迹法测定45例早发CAD患者健康后代外周血白细胞DNA端粒限制性片段（TRF）平均长度（病例后代）和59个来自无此类病史家庭的后代（对照后代）。还在67个子代-亲本对中评估了平均TRF长度的相关性。平均而言，下降27.5平均每岁TRF长度为10.7bp，未经校正的平均TRF长度为6.34kb（95% CI 6.13至6.55），对照组后代为6.75 kb（95% CI 6.57至6.94）（p = 0.004）。病例组和对照组后代之间的平均TRF校正差异为472 bp（95%CI 253至691，p < 0.001），相当于约17年的年龄相关端粒长度损耗。结论：短端粒的遗传与冠心病家族性风险增加有关。他们支持这样的假设，端粒长度是一个主要的异常参与CAD的发病机制。
Background: Telomeres are shorter in subjects with coronary artery disease (CAD) and may indicate premature biological ageing. However, whether shorter telomeres are a primary abnormality or secondary to the disease is unclear.Objective: To investigate whether shorter telomeres are a primary abnormality or secondary to CAD, telomere lengths in healthy young adults with contrasting familial risk of CAD were compared.Design: Case - control study.Methods: Mean telomere restriction fragment (TRF) length in DNA from circulating leucocytes was determined by Southern blotting in 45 healthy offspring of subjects with premature CAD (case offspring) and 59 offspring from families without such a history (control offspring). Correlation in mean TRF length was also assessed in 67 offspring - parent pairs.Results: On average, a decrease of 27.5 (10.7) bp in mean TRF per year of age was found. The unadjusted mean TRF length was 6.34 kb (95% CI 6.13 to 6.55) for case offspring and 6.75 kb (95% CI 6.57 to 6.94) for offspring of controls (p = 0.004). The adjusted difference in mean TRF between case and control offspring was 472 bp (95% CI 253 to 691, p < 0.001), equivalent to about 17 years of age-related attrition in telomere length. Furthermore, there was a significant positive correlation in mean TRF length between offspring and their parents (r = 0.37, p = 0.002).Conclusion: These findings suggest that inheritance of shorter telomeres is associated with increased familial risk of CAD. They support the hypothesis that telomere length is a primary abnormality involved in the pathogenesis of CAD.