Influence of AGT, TGFB1, ESR1, and VDR gene variants on development and course of idiopathic interstitial pneumonias and pulmonary sarcoidosis

Abstract

The aim of the study was to estimate the contribution of angiotensinogen (AGT), transforming growth factor beta-1 (TGFB1), estrogen receptor alpha (ESR1), and vitamin D receptor (VDR) gene variants to IIP and PS development and course in residents of Russian Federation. Methods. This case-control study involved 104 IIP patients, 111 PS patients, and 113 controls. Seven single nucleotide polymorphisms were investigated using polymerase chain reaction followed by restriction analysis, namely rs5051 in AGT gene; rs1800469, rs1800470, and rs1800471 in TGFB1 gene; rs2234693 and rs9340799 in ESR1 gene; rs731236 in VDR gene. Results. We revealed associations of TGFB1 (rs1800469) and ESR1 (rs9340799) gene variants with IIP clinical outcomes, as well as AGT (rs5051) and VDR (rs731236) gene variants with PS stage. Unfavorable IIP outcomes, i.e. IIP progression or death, were associated with variants rs1800469 СС in TGFB1 gene (р = 0.021; odds ratio (OR) = 2.83; 95%CI: 1.16–6.94) and rs9340799 X (G) in ESR1 gene (р = 0.012; OR = 3.18; 95%CI: 1.27–8.00), as well as with their combination (р = 0.003; OR = 3.88; 95%CI: 1.55–9.71). PS stages II–IV were associated with variants rs5051 А in AGT gene (р = 0.010; OR = 3.22; 95%CI: 1.30–7.98) and rs731236 t (C) in VDR gene (р = 0.046; OR = 2.45; 95%CI: 1.00–6.02), as well as with their combination (р = 0.041; OR = 3.31; 95%CI: 1.14–9.60). Conclusion. Results of the study contribute to understanding genetic factors that influence IIP and PS courses.