Analysis of Genetic Variation in CD40 and CD40L: Relationship with mRNA Relative Expression and Soluble Proteins in Acute Coronary Syndrome.

D E Martínez-Fernández,J F Muñoz-Valle,Y Valle,U Zalapa Flores,Maricela Aceves-Ramírez,Emmanuel Valdés-Alvarado,Brenda Parra-Reyna,J C Chávez Herrera,J R Padilla-Gutiérrez,F Casillas-Muñoz

doi:10.1155/2019/8063983

Abstract

Acute coronary syndrome (ACS) can be triggered by the presence of inflammatory factors which promote the activation of immune cells by costimulatory molecules such as CD40 and its ligand CD40L. Environmental and genetic factors are involved in the etiology of the ACS. The aim of this study was to explore the gene and protein expression associated with CD40 and CD40L genetic variants in ACS patients from the western Mexican population. A total of 620 individuals from western Mexico were recruited: 320 ACS patients and 300 individuals without a history of ischemic cardiopathy were evaluated. The genotype was determined using TaqMan SNP genotyping assays. CD40 and CD40L expressions at the mRNA level were quantified using TaqMan Gene Expression Assays. Soluble protein isoforms were measured by enzyme-linked immunosorbent assay. We did not find evidence of association between CD40 (rs1883832, rs4810485, and rs11086998) and CD40L (rs3092952 and rs3092920) genetic variants and susceptibility to ACS, although rs1883832 and rs4810485 were significantly associated with high sCD40 plasma levels. Plasma levels of sCD40L can be affected by gender and the clinical spectrum of acute coronary syndrome. Our results do not suggest a functional role of CD40 and CD40L genetic variants in ACS. However, they could reflect the inflammatory process and platelet activation in ACS patients, even when they are under pharmacological therapy. Due to the important roles of the CD40-CD40L system in the pathogenesis of ACS, longitudinal studies are required to determine if soluble levels of CD40 and CD40L could be clinically useful markers of a recurrent cardiovascular event after an ACS.

Highlights

Cardiovascular disease is the leading cause of death worldwide [1], acute coronary syndrome (ACS) characterized by the acute reduction in coronary blood flow and myocardial ischemia or necrosis
It is important to mention that we explored the CD40L mRNA expression in both groups of study according to genetic variants, following the dominant model; we did not find differences
This polymorphism has been associated with diminished mRNA expression of CD40 [21, 22]; rs1883832 has been found in high linkage disequilibrium (LD) with rs4810485, the latter being significantly associated with coronary artery lesion formation in a Taiwanese population [33]

Summary

Introduction

Cardiovascular disease is the leading cause of death worldwide [1], acute coronary syndrome (ACS) characterized by the acute reduction in coronary blood flow and myocardial ischemia or necrosis. Journal of Immunology Research reason, the early prognosis and risk stratification are the first line of action to reduce the risk of recurrent episodes or even death after an ACS [3]. In the etiology of ACS, metabolic, genetic, environmental, and among other factors are involved, conditions that can increase inflammation and endothelial dysfunction, key elements in the development of atherosclerosis [4, 5]. CD40 is a costimulatory molecule that is expressed constitutively in B lymphocytes and expressed in other cells such as monocytes, macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs) [7]. CD40L, is expressed mainly on the surface of platelets (95%), T lymphocytes, ECs, SMCs, and macrophages [7, 8]

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