Influence of Pentraxin 3 (PTX3) Genetic Variants on Myocardial Infarction Risk and PTX3 Plasma Levels

Abstract

PTX3 is a long pentraxin of the innate immune system produced by different cell types (mononuclear phagocytes, dendritic cells, fibroblasts and endothelial cells) at the inflammatory site. It appears to have a cardiovascular protective function by acting on the immune-inflammatory balance in the cardiovascular system. PTX3 plasma concentration is an independent predictor of mortality in patients with acute myocardial infarction (AMI) but the influence of PTX3 genetic variants on PTX3 plasma concentration has been investigated very little and there is no information on the association between PTX3 variations and AMI. Subjects of European origin (3245, 1751 AMI survivors and 1494 controls) were genotyped for three common PTX3 polymorphisms (SNPs) (rs2305619, rs3816527, rs1840680). Genotype and allele frequencies of the three SNPs and the haplotype frequencies were compared for the two groups. None of the genotypes, alleles or haplotypes were significantly associated with the risk of AMI. However, analysis adjusted for age and sex indicated that the three PTX3 SNPs and the corresponding haplotypes were significantly associated with different PTX3 plasma levels. There was also a significant association between PTX3 plasma concentrations and the risk of all-cause mortality at three years in AMI patients (OR 1.10, 95% CI: 1.01–1.20, p = 0.02). Our study showed that PTX3 plasma levels are influenced by three PTX3 polymorphisms. Genetically determined high PTX3 levels do not influence the risk of AMI, suggesting that the PTX3 concentration itself is unlikely to be even a modest causal factor for AMI. Analysis also confirmed that PTX3 is a prognostic marker after AMI.

Association of the long pentraxin PTX3 gene polymorphism (rs3816527) with migraine in an Iranian population

“…For instance about rs3816527, plasma PTX3 levels were higher in only CC carrier controls. In summary this study showed that genetically determined high PTX3 levels do not affect the risk of AMI [31].…”

Pentraxin‐3 level at admission is a strong predictor of short‐term mortality in a community‐based hospital setting

“…The results of previous studies have suggested that some biomarkers, including PTX3, perform better when used in combination rather than individually. This is true for PTX3 combined with pro-BNP [26,35] or troponin T [33,36,42] in patients with heart disease. Similarly, a combinatorial approach for diagnosing sepsis with a 'bioscore' comprising three markers, neutrophil CD64 index, procalcitonin (PCT; a marker of infection) and a soluble triggering receptor on myeloid cells-1 (sTREM-1), has been shown to be clinically useful [43].…”

“…Recent findings in this field have suggested that PTX3 is an independent marker of disease activity and mortality in patients with acute coronary syndrome [2,[32][33][34][35], chronic heart failure [36][37][38], coronary heart disease [39] and cardiac syndrome X [40]. Cumulative survival Fig.…”

The Long Pentraxin PTX3 as a Key Component of Humoral Innate Immunity and a Candidate Diagnostic for Inflammatory Diseases

“…In addition, PTX3 polymorphisms were recently associated with protein levels and susceptibility to A. fumigatus infection in two cohorts of patients undergoing bone marrow transplantation [72]. PTX3 plasma levels were found to be associated with three genetic polymorphisms [73]. Accordingly, a recent study has suggested that PTX3 polymorphisms may alter mRNA stability, leading to decreased expression of PTX3, impaired phagocytosis and clearance of A. fumigatus in neutrophils [72].…”