Association of the TNFRSF1A genotype with lung function impairment in patients with sarcoidosis

The single-nucleotide polymorphism (SNP) rs1800693 in the tumor necrosis factor receptor 1 (TNFR1) gene leads to the formation of a protein-mimicking effect of TNF-α inhibitors, which are agents used to treat sarcoidosis. We investigated the association between rs1800693 and disease progression in two populations with non-Lofgren sarcoidosis (nLS). We genotyped two nLS cohorts (Ruhrlandklinik, Germany, n = 108, and the HUNT study, Norway, n = 393), and two control groups with (n = 313) and without (n = 2414) COPD for rs1800693 (A/G polymorphism). Pulmonary function tests at inclusion and at the end of follow-up were compared according to genotype. The mean follow-up times were 6.5 (German) and 7.9 (Norwegian) years. German AA patients had an absolute decline in %pred FVC (-8.5, 95% CI -3.4, -13.6) and DLco (-4.9, 95% CI -0.1, -9.7). In AG/GG (G+), the absolute decline in FVC was less pronounced (-3.9, 95% CI -1.1, -6.8), and DLco was stable. In the Norwegian patients, the decrease in lung function was similar between the AA and G+ groups. Compared with homozygous GG, homozygous AA was associated with a lower FVC %pred at baseline (-5.7, 95% CI -0.2, -11.6) and at the end of follow-up (-7.0, 95% CI -0.1, -14.0). Genotype was not associated with lung function in either control group. TNFR1 rs1800693 might be associated with lung function impairment and decline in non-Lofgren sarcoidosis patients.