insertion polymorphism in the gene impairs mitochondrial DNA maintenance and affects the age of onset of IPF.

BACKGROUND

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.

RESULTS

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.

METHODS

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 .

CONCLUSIONS

The insertion polymorphism in impairs mtDNA stability and affects the age of onset of IPF.