Relating interferon regulatory factor 5 rs2004640 gene polymorphism to increased risk of systemic sclerosis in the patients: Russian Federation cohort

Background ― A number of studies confirmed a crucial role of type 1 interferon in pathophysiology of connective tissue diseases. Interferon regulatory factors (IRF) coordinate an expression of type 1 interferon, while interferon regulatory factor 5 (IRF5) gene was recently identified as causing predisposition to systemic lupus erythematosus and Sjögren syndrome. The objective of our study was to identify possible association of IRF5 rs2004640 (G/T) single nucleotide polymorphism with systemic sclerosis (SSc). Material and Methods―The study involved 236 individuals, including 105 patients with SSc diagnosis and 131 control individuals from Moscow region. The latter were healthy, unrelated to each other, their genders and ages were matched to those of SSc patients. Allele-specific real-time polymerase chain reaction (PCR) was used to study IFR5 rs2004640 polymorphism. Results ― We detected significantly higher percentage of IRF5 T-allele carriers in all patients (59.5%), those with diffuse cutaneous SSc (67.3%), patients with interstitial lung lesions (62.3%), and those with positive titers of anti-topoisomerase I antibodies (66.3%), compared with control group (46.2%). The odds ratios (OR) were: 1.71 (р=0.00), 2.40 (р=0.0004), 1.93 (р=0.002), and 2.30 (р=0.0008), correspondingly. Conclusion ― The replacement of nucleotide G by T in the IRF5 rs2004640 gene polymorphism was associated with a predisposition to SSc. Our data implied an existence of a novel SSc pathogenetic pathway associated with important role of type 1 interferon in pathophysiology of connective tissue diseases.