Zhou Wei, Sun Jiapeng, Guo Wenwen, Zhuang Yi, Xu Lizhi, Wang Yaping
Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China.
Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
Aging (Albany NY). 2019 Feb 4;11(3):933-949. doi: 10.18632/aging.101793.
Idiopathic pulmonary fibrosis (IPF) is an age-related fatal disease with an unknown etiology. Increased oxidative stress and mitochondrial dysfunction are thought to be involved in its pathogenesis. However, the effect of the polymorphism on IPF is not known.
The mean age of onset for IPF in patients homozygous for the variant () was 66.5 years old, which was significantly earlier than that in patients with the wild-type (, 70.45 years old). For the 97 male IPF patients with lung function data, the FVC% of the patients was lower than that of the wild-type ( or heterozygous () patients. The laboratory analysis indicated that an increased mtDNA content and impaired mitochondrial quality control were associated with the genotype. We also confirmed that insertion into caused decreased MUTYH1 expression in lung tissues.
We compared the lung function of IPF patients and observed the mtDNA content, mtDNA integrity and molecular expression of mitochondrial quality control among subjects with different genotypes. Additionally, immunoblotting and a reporter gene system were used to test whether altered mitochondrial MUTYH1 expression was linked to .
The insertion polymorphism in impairs mtDNA stability and affects the age of onset of IPF.
特发性肺纤维化（IPF）是一种与年龄相关的致命疾病，病因不明。氧化应激增加和线粒体功能障碍被认为参与其发病机制。然而，该多态性对IPF的影响尚不清楚。
该变异（）纯合子的IPF患者平均发病年龄为66.5岁，显著早于野生型患者（，70.45岁）。对于97例有肺功能数据的男性IPF患者，该患者的用力肺活量百分比（FVC%）低于野生型（或杂合子（）患者。实验室分析表明，线粒体DNA（mtDNA）含量增加和线粒体质量控制受损与该基因型有关。我们还证实，插入到中会导致肺组织中MUTYH1表达降低。
我们比较了IPF患者的肺功能，并观察了不同基因型受试者的mtDNA含量、mtDNA完整性和线粒体质量控制的分子表达。此外，采用免疫印迹和报告基因系统来检测线粒体MUTYH1表达改变是否与有关。
中的插入多态性损害mtDNA稳定性并影响IPF的发病年龄。
