Distinct Differences Seen in Mucus-encoding Genes of IPF Patients Across Europe

Certain distinctive genetic differences or variations, including in genes involved in mucus production, were found to be significantly predominant in European populations of patients with idiopathic pulmonary fibrosis (IPF), according to the study, “Association Study for 26 Candidate Loci in Idiopathic Pulmonary Fibrosis Patients from Four European Populations” published in the journal Frontiers in Immunology.

IPF is a chronic and progressive lung disease. Despite its unknown causes, several reports have suggested that multiple genetic factors are involved in IPF development. The team of researchers recently identified 26 gene variants (called single nucleotide polymorphisms, SNPs, a difference in a single nucleotide that occurs at a specific position in the genome) as potentially associated with IPF. These variants are linked to several cellular pathways (including mucin production, cell-cycle regulation, and pro-inflammatory and profibrotic signaling pathways). Mucins are the major constituents of normal mucus, a barrier that provides protection for the epithelial cells that line the respiratory and gastrointestinal tract.

Now, these researchers, from across Europe, investigated whether the 26 IPF candidate genetic variants might indeed exist in IPF patients in four different European populations – Czech, German, Greek, and French – representing Central, Southern, and Western Europe.

The team enrolled 165 IPF patients (41 Czechs, 33 Germans, 40 Greeks, and 51 French). They isolated genomic DNA from patients’ peripheral blood leukocytes, or white blood cells. The DNA was sequenced, and researchers analyzed the distribution of the 26 variants in all four populations.

They found a significant statistical association between one variant (rs35705950) of mucin encoding MUC5B gene and IPF susceptibility in all of these groups. Another variant (rs7934606) in the MUC2 gene was significant among German patients and combined European IPF cases. Notably, the MUC5B rs35705950 variant was also reported in a previous study to be present in U.S. populations of European descent. Other variants also positively associated with either individual European populations (TP53 rs12602273, ACE-II rs4277405, ACE-II rs4459609, TERT rs2736100, ATP11A rs1278769, and IL-1α rs1800587), or with the general population, specifically MUC2 (rs79834606) and TF (rs1799899).

Overall, the results strongly linked mucin-encoding gene variants with IPF in European populations and in those of European descent. Additional studies are required to fully understand the association of other variants to IPF, and to determine whether these genetic variants can be used as IPF genetic risk markers.