Remes A M, Hassinen I E, Ikäheimo M J, Herva R, Hirvonen J, Peuhkurinen K J
Department of Medical Biochemistry, University of Oulu, Finland.
J Am Coll Cardiol. 1994 Mar 15;23(4):935-42. doi: 10.1016/0735-1097(94)90640-8.
The aim of this study was to assess the occurrence of the two most commonly encountered mitochondrial DNA (mtDNA) deletions in the hearts of patients with idiopathic dilated cardiomyopathy.
The mutation frequency of mtDNA is high, and sporadic cases of cardiomyopathies associated with mtDNA deletions have been described. Reports of increases in mtDNA deletions with advancing age also exist.
We studied 15 consecutive patients with typical signs of idiopathic dilated cardiomyopathy, without a family history, together with 16 control hearts obtained at autopsy from patients who died of noncardiac causes. The patients underwent both right and left heart catheterization, during which endomyocardial biopsy samples were taken. The mtDNA in these samples and in the control hearts was analyzed by the polymerase chain reaction technique for the occurrence and proportion of 5- and 7.4-kilobase (kb) deletions (Cambridge sequence map positions from nucleotides 8469 to 13447 and 8637 to 16084, respectively).
The 5-kb mtDNA deletion was observed in the hearts of all of the patients with idiopathic dilated cardiomyopathy, accounting for 0.32 +/- 0.05% (mean +/- SEM) of the total mtDNA. The 7.4-kb deletion was found in 7 of the 15 patients with idiopathic dilated cardiomyopathy and comprised 0.28 +/- 0.08% of the total. The 5- and 7.4-kb deletions were detected in 12 and 9 control hearts, respectively, quantitatively similar to the patients with idiopathic dilated cardiomyopathy. A sigmoidal age dependency of the mtDNA deletions was found both in the patients with cardiomyopathy and in the control hearts, but after elimination of the confounding age variable, there was no difference between these groups.
Because of the similarity of the age-dependent increase in the frequency of mtDNA deletions in cardiomyopathic and control hearts, the deletions have no causal relation with idiopathic dilated cardiomyopathy. The present results confirm the notion of an increase in mtDNA deletions with advancing age and show that endomyocardial tissue sampling is a feasible method for detecting mtDNA defects in affected hearts.
本研究旨在评估特发性扩张型心肌病患者心脏中两种最常见的线粒体DNA（mtDNA）缺失的发生率。
mtDNA的突变频率很高，并且已经有散发性与mtDNA缺失相关的心肌病病例报道。也有关于随着年龄增长mtDNA缺失增加的报道。
我们研究了15例连续的无家族病史的典型特发性扩张型心肌病患者，以及16例从死于非心脏原因的患者尸检中获得的对照心脏。患者接受了右心和左心导管检查，在此期间采集了心内膜活检样本。通过聚合酶链反应技术分析这些样本和对照心脏中的mtDNA，以检测5千碱基（kb）和7.4 kb缺失（分别对应剑桥序列图谱中核苷酸8469至13447和8637至16084的位置）的发生率和比例。
在所有特发性扩张型心肌病患者的心脏中均观察到5 kb的mtDNA缺失，占总mtDNA的0.32±0.05%（平均值±标准误）。在15例特发性扩张型心肌病患者中的7例中发现了7.4 kb的缺失，占总量的0.28±0.08%。在12例和9例对照心脏中分别检测到5 kb和7.4 kb的缺失，在数量上与特发性扩张型心肌病患者相似。在心肌病患者和对照心脏中均发现mtDNA缺失呈S形年龄依赖性，但在消除混淆的年龄变量后，这些组之间没有差异。
由于心肌病患者和对照心脏中mtDNA缺失频率随年龄增长的相似性，这些缺失与特发性扩张型心肌病没有因果关系。目前的结果证实了随着年龄增长mtDNA缺失增加的观点，并表明心内膜组织采样是检测受影响心脏中mtDNA缺陷的可行方法。
