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IL17RA in early-onset coronary artery disease: Total leukocyte transcript analysis and promoter polymorphism

Eliecer Coto1, Isaac Pascual2, Pablo Avanzas2

  • 1Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, Oviedo, Spain; Departamento Medicina, Universidad de Oviedo, Oviedo, Spain; Red de Investigación Renal (REDINREN), Madrid, Spain.

Cytokine
|September 19, 2020
PubMed

Insights

The interleukin-17 receptor A (IL-17RA) transcript is significantly higher in leukocytes of coronary artery disease (CAD) patients, suggesting a role for the IL-17 pathway in atherosclerosis. Genetic variations in IL-17RA were not associated with CAD risk.

Area of Science:

  • Immunology
  • Cardiovascular Medicine
  • Genetics

Background:

  • The interleukin-17 (IL-17) pathway is implicated in atherosclerosis and coronary artery disease (CAD).
  • Th17 cells expressing IL-17 inflammatory mediators infiltrate vascular tissue, influencing atherosclerotic lesion development.
  • Cigarette smoke exposure increases IL-17 and IL-17 receptor expression, and IL-17RA deficiency reduces lesion size in mouse models.

Purpose of the Study:

  • To investigate the differential expression of the IL-17RA transcript in leukocytes from CAD patients and healthy individuals.
  • To examine the association of IL-17RA promoter polymorphisms with CAD.

Main Methods:

  • Quantified IL-17RA transcript levels relative to ACTB in leukocytes from 55 CAD patients and 50 healthy smokers.
  • Genotyped IL-17RA rs48195554 promoter polymorphisms in 390 healthy controls and 450 early-onset CAD patients.

Main Results:

  • CAD patients exhibited significantly higher normalized IL-17RA transcript levels compared to controls (p < 0.001).
  • IL-17RA G-carriers showed elevated transcript values, but allele and genotype frequencies of rs48195554 did not differ between CAD patients and controls.
  • No significant association was found between IL-17RA promoter polymorphisms and CAD.

Conclusions:

  • Elevated IL-17RA transcript levels in CAD patients support the involvement of the IL-17 pathway in coronary atherosclerosis pathogenesis.
  • IL-17RA gene polymorphisms are unlikely to be a major genetic risk factor for CAD in this cohort.
Abstract

Keywords:
AtherosclerosisCoronary Artery DiseaseGene polymorphismsGenetic associationIL17 pathway

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