Citrullinated and MMP-degraded vimentin is associated with chronic pulmonary diseases and genetic variants in PADI3/PADI4 and CFH in postmenopausal women: an observational study

Abstract

Abstract Background Citrullinated vimentin has been linked to several chronic and autoimmune diseases, but how citrullinated vimentin is associated with disease prevalence and genetic variants in a clinical setting remains unknown. The aim of this study was to obtain a better understanding of the genetic variants and pathologies associated with citrullinated and MMP-degraded vimentin. Methods Patient Registry data, serum samples and genotypes were collected for a total of 4369 Danish post-menopausal women enrolled in the Prospective Epidemiologic and Risk Factor study (PERF) Circulating citrullinated and MMP-degraded vimentin (VICM) was quantified using -a well-established biomarker assay. Genome-wide association (GWAS) with serum levels of VICM and Phenome Wide Association (PheWAS) with the identified polymorphisms were performed. Results High levels of VICM was significantly associated with the prevalence of chronic pulmonary diseases and death from respiratory and cardiovascular diseases (CVD). GWAS identified 33 single nucleotide polymorphisms (SNPs) with a significant association to VICM. These variants were in the peptidylarginine deiminase 3/4 (PADI3/PADI4) and Complement Factor H (CFH)/ KCNT2 gene loci on chromosome 1. Conclusion Serum levels of VICM, a marker of citrullinated and MMP-degraded vimentin, were associated with chronic pulmonary diseases and genetic variance in PADI3/PADI4 and CFH/ KCNT2. This points to the potential for VICM to be used as an activity marker of both citrullination and inflammation identifying responders to targeted treatment and patients likely to experience disease progression.