检测特发性肺纤维化和结节病患者中线粒体转移 RNA(mt-tRNA)基因突变。

Detection of mitochondrial transfer RNA (mt-tRNA) gene mutations in patients with idiopathic pulmonary fibrosis and sarcoidosis.

机构信息

Department of Respiratory Medicine, University of Thessaly School of Medicine, University Hospital of Larissa, BIOPOLIS, Larissa 41110, Greece.

出版信息

Mitochondrion. 2018 Nov;43:43-52. doi: 10.1016/j.mito.2018.10.004. Epub 2018 Oct 26.

DOI:10.1016/j.mito.2018.10.004

PMID:30473003

Abstract

Mitochondrial reactive oxygen species production may lead to tissue injury associated with two respiratory disorders of unknown origin which are shared by common tissue fibrosis, IPF and sarcoidosis. Sequence analysis of 22 mt-tRNA genes and parts of their flanking genes revealed 32 and 45 mutations in 38/40 IPF and 69/85 sarcoidosis patients respectively. 4 novel mutations were identified. 15/32 and 25/45 mutations were exclusively expressed while 12/32 and 17/45 mutations predominantly occurred in IPF and sarcoidosis group respectively, compared to healthy controls. Novel mutation combinations were solely expressed in disease. Hence, a mitochondrial-mediated pathogenic pathway seems to underlie both entities.

摘要

线粒体活性氧的产生可能导致与两种未知起源的呼吸疾病相关的组织损伤，这两种疾病在特发性肺纤维化（IPF）和结节病中共同存在，具有共同的组织纤维化。对 22 个 mt-tRNA 基因及其侧翼基因的部分序列分析显示，在 40 名 IPF 患者和 85 名结节病患者中分别发现了 32 个和 45 个突变。鉴定出 4 个新突变。与健康对照组相比，15/32 和 25/45 个突变仅在 IPF 和结节病组中表达，而 12/32 和 17/45 个突变则主要在 IPF 和结节病组中发生。新的突变组合仅在疾病中表达。因此，一种线粒体介导的致病途径似乎是这两种疾病的基础。