Atrial fibrillation is associated with accumulation of aging-related common type mitochondrial DNA deletion mutation in human atrial tissue
Atrial fibrillation is associated with accumulation of aging-related common type mitochondrial DNA deletion mutation in human atrial tissue
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DOI：
10.1378/chest.123.2.539
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发表时间：
2003-02-01
期刊：
影响因子：
9.6
通讯作者：
Huang, SKS
中科院分区：
文献类型：
--
作者：
Lai, LP;Tsai, CC;Huang, SKS
研究目的：线粒体DNA(mitocihondrial DNA，mtDNA)体细胞突变的积累与衰老和进行性器官功能障碍有关。我们研究了人心房组织线粒体DNA 4977碱基缺失突变(mtDNA(4977))，并将其与临床心房颤动(房颤)的关系进行了研究。方法与结果：88例心内直视手术患者(儿童/青少年22例，成人66例)，均取右心耳组织。用套式聚合酶链式反应方法测量mtDNA4977的量，并将其归一化为野生型mtDNA。我们发现mtDNA4977在所有22名儿童/青少年患者中都缺失。在成人组中，房颤患者mtDNA4977的相对数量显著高于非房颤患者(0.55+/-0.26vs0.35+/-0.29，p<；0.007)[Mean+/-SD]。线粒体DNA含量(4977)与年龄呈正相关(r=0.29，p<；0.01)。左、右房压力、左房内径、高血压和心脏病诊断对mtDNA(4977)的量没有显著影响。进一步的多因素分析显示，增龄和房颤对mtDNA的积累起独立作用。结论：房颤与mtDNA(4677)的增加有关。这种变化类似于心房组织的衰老过程，可能是房颤时心房功能障碍的原因之一。
Study objective: Accumulation of somatic mutations of mitocihondrial DNA (mtDNA) contributes to the aging process and progressive organ dysfunction. We investigated the mitochondrial DNA with 4977-base-pair mtDNA deletion mutation (mtDNA(4977)) in human atrial tissue and correlated the amount of mtDNA 4977 to clinical atrial fibrillation (AF).Methods and results: Atrial tissue from the right atrial appendage was obtained in 88 patients during open-heart surgery (22 children/adolescents and, 66 adults). The amount of mtDNA4977 was measured using a nested polymerase chain reaction protocol and normalized to wild-type mtDNA. We found that the mtDNA4977 was absent in all 22 pediatric/adolescent patients. In the adult group, the relative amount of mtDNA4977 was significantly higher in patients with AF than in patients without AF (0.55 +/- 0.26 vs 0.35 +/- 0.29, p < 0.007) [mean +/- SD]. The amount of mtDNA(4977) was also positively associated with age (r = 0.29, p < 0.01). Left and right atrial pressures, left atrial dimension, hypertension, and cardiac diagnosis did not influence the amount of mtDNA(4977) significantly. Further multivariate analysis showed that both aging and AF contributed independently to the accumulation of mtDNAConclusion: AF is associated with an increase of mtDNA(4677). This change is similar to the aging process of atrial tissue and might contribute to atrial dysfunction in AF.