Interferon-γ and interferon-γ receptor 1 and 2 gene polymorphisms and restenosis following coronary stenting

• Published in: Atherosclerosis 2005-09, Vol.182 (1), p.145-151
• Main Authors: Tiroch, K., von Beckerath, N., Koch, W., Lengdobler, J., Joost, A., Schömig, A., Kastrati, A.
• Format: Article
• Language: English
• Subjects: Aged; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Coronary heart disease; Coronary Restenosis - epidemiology; Coronary Restenosis - genetics; Coronary Stenosis - epidemiology; Coronary Stenosis - genetics; Coronary Stenosis - therapy; Female; Genetic Predisposition to Disease - epidemiology; Genetics; Genotype; Heart; Humans; Incidence; Interferon gamma Receptor; Interferon-gamma - genetics; Interferon-γ; Male; Medical sciences; Middle Aged; Polymorphism, Genetic; Postoperative Complications; Receptor; Receptors, Interferon - genetics; Restenosis; Stents; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2005.02.003

In a recent study, analysis of gene expression in atherectomy specimens derived from restenotic coronary lesions revealed 223 differentially expressed genes. Thirty-seven of these genes indicated activation of interferon- (IFN-) γ signaling in neointimal smooth muscle cells. Moreover, genetic disruption of IFN-γ signaling in a mouse model of restenosis significantly reduced the vascular proliferative response. Thus, IFN-γ is assumed to play an important role in the control of tissue proliferation during neointima formation. We hypothesized that genetic variants of IFN-γ and its receptor subunits are involved in upregulation of IFN-γ related genes in neointimal tissue of patients that develop in-stent restenosis. Polymorphisms in the genes encoding for IFN-γ (IFNG T874A) and its receptors 1 (IFNGR1 C-56T) and 2 (IFNGR2 A839G) were tested for their association with restenosis. IFNG T874A, IFNGR1 C-56T and IFNGR2 A839G genotypes were determined in a consecutive series of patients ( n = 2591) that had been treated with coronary stents. Follow-up angiography 6 months after stent implantation was performed in 76.8% of the patients. Genotyping was performed with PCR-based methods. IFNG T874A, IFNGR1 C-56T and IFNGR2 A839G genotypes were not associated with the incidence of angiographic and clinical restenosis ( P > 0.23). Moreover, there was no association between IFNG, IFNGR1 and IFNGR2 genotypes and the combined incidence of death form any cause and non-fatal myocardial infarction during the first 12 months following the intervention ( P > 0.61). Thus, this study does not support a clinically relevant role of the studied polymorphisms in the processes leading to in-stent restenosis.