Genetic Analysis Of Familial Idiopathic Pulmonary Fibrosis

[OBJECTIVE] Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory interstitial lung disease with an unknown cause. Recent studies have shown that genetic factors play an important role in the pathogenesis of IPF. This study aimed to explore the role of genetic factors in the pathogenesis of idiopathic pulmonary fibrosis by pedigree genetic analysis, providing meaningful evidence for the mechanism of IPF in Chinese population and theoretical bases for new clinical treatments for the disease. As control groups, a number of patients and healthy people were screened for these sites to find associations with IPF.[METHODS] To explore the genetic background of patients with IPF, a candidate gene approach was employed to screen for mutations in seven genes among ten members with familial idiopathic pulmonary fibrosis (FPF) in mainland China. All the mutant sites were verified with bioinformatics analysis and functinonal annotation.[RESUILS] Within six of the candidate genes, a total of31point mutations were identified. Among the missense mutations, the SFTPA1exon6CAG>AAG (Gln238Lys) and SFTPB exon2CAC>CCC (His2Pro) mutations caused changes in the physical and chemical properties of amino acids. Each sequence alteration was identified in sporadic IPF patients, control specimens (pneumonia patients and healthy persons). Genotype frequencies and allele frequencies of codon238in exon6of SFT PA1were noted significantly higher in patients with IPF than those in other two control subjects. The computational protein structure prediction by protein theading confirmed differences in three-dimensional structure between mutant SFTPA1and original SFTPA1.[CONCLUSION] Although the functions of the mutant candidate genes are different, these genes may ultimately result in the alveolar epithelial cells injury, which initiate the pulmonary fibrosis progress. In particular, while pathophysiological mechanisms needs to be illustrated, that the Gln238Lys mis sense variant of exon6in the SFTPA1may have potential susceptibility in the development of IPF, which was shown in patients with sporadic IFP with a statistically higher frequency.