Genetic landscape of idiopathic pulmonary fibrosis: A systematic review, meta-analysis and epidemiological evidence of case-control studies

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fibrotic lung disorder of unknown cause, affecting about three million people worldwide. Being a multifactorial disease, complex genetic and environmental factors contribute to its susceptibility. Therefore, we conducted a two-staged systematic literature search and meta-analyses of published genetic association studies on IPF. MethodsThe first search was performed using PubMed and Web of Science, retrieving a total of 5642 articles, of which 57 publications were eligible for inclusion in the first stage. The Second search was performed using PubMed, Web of Science and Scopus for all genetic variants, identified from the first search, with 2 or more studies. Thus, six variants [rs35705950 (MUC5B), rs2736100 (TERT), rs2609255 (FAM13A), rs2076295 (DSP), rs12610495 (DPP9) and rs1800470 (TGF-{beta}1)] from this search qualified for meta-analyses. Additionally, the epidemiological credibility of these six variants was evaluated using the Venice criteria. ResultsIn this systematic review, 291 polymorphisms were found to be associated with IPF susceptibility. Meta-analyses findings revealed significant (p < 0.05) risk association of rs35705950 [T vs C; OR = 3.85(3.24-4.47)], rs2609255 [G vs T; OR = 1.37(1.27-1.47)], rs2076295 [G vs T; OR = 1.31(1.00-1.63)], rs12610495 [G vs A; OR = 1.29(1.21-1.37)] and rs1800470 [T vs C; OR = 1.08(0.82-1.34)] and protective association of rs2736100 [C vs A; OR = 0.70(0.61-0.79)] with IPF susceptibility. Cumulative epidemiological evidence was graded as strong for rs35705950, moderate for rs2736100, rs2609255 and rs12610495, and weak for rs2076295 and rs1800470. ConclusionsOur findings present the most prominent IPF-associated genetic risk variants involved in alveolar epithelial injuries (MUC5B, TERT, FAM13A, DSP, DPP9) and epithelial-mesenchymal transition (TGF-{beta}1), providing genetic and biological insights into IPF pathogenesis.