IL17RA in early-onset coronary artery disease: Total leukocyte transcript analysis and promoter polymorphism (rs4819554) association. (December 2020)

• Record Type: Journal Article
• Authors: Coto, Eliecer; Pascual, Isaac; Avanzas, Pablo; Cuesta-Lavona, Elías; Lorca, Rebeca; Martín, María; Vázquez-Coto, Daniel; Díaz-Corte, Carmen; Morís, César; Rodríguez-Reguero, Julián; Gómez, Juan
• Is Part Of: Cytokine. Volume 136(2020)
• Publication Date: 2020-12
• Subjects: Coronary Artery Disease -- Atherosclerosis -- IL17 pathway -- Gene polymorphisms -- Genetic association; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155285
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: The IL17 pathway is important in the development of atherosclerotic plaques. IL17A/17RA polymorphisms have been associated with inflammatory diseases. We did not find difference between Il17 variants in coronary disease and controls. The Il-17RA was significantly overexpressed in leukocytes from patients. Abstract: Background and aims: The interleukin-17 (IL-17) pathway would play an important role in the pathogenesis of atherosclerosis and coronary-artery disease (CAD). The IL-17 inflammatory mediators are expressed by Th17 cells, a group of CD4 + leukocytes that infiltrate the vascular milieu and are pivotal in the origin, progression, stability and rupture of the atherosclerotic lesion. Cigarette smoke compounds stimulated the expression of IL-17 and IL-17-receptors. In atherogenic mice models the deficiency of IL-17RA resulted in a reduction of the atherosclerotic lesion size and leukocyte infiltrate. We hypothesised that common the IL-17RA transcript might be differential expressed in the leukocytes from CAD patients and healthy individuals. Methods: The relative amount of the IL-17RA to ACTB transcript was determined in total leukocytes of 55 patients and 50 controls, all smokers. We genotyped the IL-17RA rs48195554 promoter polymorphisms in 390 healthy controls and 450 early-onset CAD patients. Results: Patients showed significantly higher mean IL-17RA normalised transcript value than controls (p < 0.001). For the IL-17RA rs48195554 promoter polymorphisms, IL-17RA G-carriers showed higher transcript values. However, allele and genotype frequencies did not differ between patients and controls and we thus excluded a significant association with CAD. Conclusions: The higher levels of the IL-17RA transcript among CAD-patients was in agreement with a role for the IL-17 pathway in the pathogenesis of coronary atherosclerosis.