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.

Figure 1. PTX3 gene details. Gene map with position of SNPs typed and inter-marker distances.

Figure 2. Distribution of PTX3 levels in 704 AMI patients in relation to the time of blood collection.

Blood samples were collected from 5 to 733 days after the AMI. This range was divided into tertiles: the first from 5 to 63 days, the second from 64 to 184 days and the third from 185 to 733 days. The mean PTX3 concentration was calculated for each tertile.

Figure 3. Histograms of the mean PTX3 levels in AMI patients and controls in relation to genotype.

Each graph shows the mean PTX3 levels (ng/mL), adjusted for sex and age, in AMI patients and controls according to rs2305619, rs3816527 and rs1840680 genotypes.