Among eight SSc-associated susceptibility polymorphisms which were applied for meta-analysis, IRF5rs2004640 polymorphism (OR 1.12; 95% CI 1.02-1.22, P = 1.39 × 10<sup>-2</sup>), STAT4 rs7574865 polymorphism (OR 1.25; 95% CI 1.07-1.47, P = 5.3 × 10<sup>-3</sup>), IRAK1 rs1059702 polymorphism (OR 1.20; 95% CI 1.05-1.37, P = 0.007), and CTGF G-945C polymorphism (OR 1.42; 95% CI 1.18-1.71, P = 0.002) are associated with PF status in SSc, while TNFAIP3 rs5029939, CD226 rs763361, CD247 rs2056626, and IRF5 rs10488631 polymorphisms are not.
We report that increased activity of the endocannabinoid/CB1R system parallels disease progression in the lungs of patients with idiopathic PF and in mice with bleomycin-induced PF and is associated with increased tissue levels of interferon regulatory factor-5.