Abstract
High levels of TREM-1 are associated with cardiovascular and inflammatory diseases risks and the most recent studies have showed that TREM-1 deletion or blockade is associated with up to 60% reduction of the development of atherosclerosis. So far, it is unknown whether the levels of TREM-1 protein are genetically regulated. Moreover, TREM family receptors have been suggested to regulate the cellular adhesion process. The goal of this study was to investigate whether polymorphisms within TREM-1 are regulating the variants of serum TREM-1 levels and the expression levels of their mRNA. Furthermore, we aimed to point out associations between polymorphisms on TREM-1 and blood levels of selectins. Among the 10 SNPs studied, the minor allele T of rs2234246, was associated with increased sTREM-1 in the discovery population (p-value = 0.003), explaining 33% of its variance, and with increased levels of mRNA (p-value = 0.007). The same allele was associated with increased soluble L-selectin levels (p-value = 0.011). The higher levels of sTREM-1 and L-selectin were confirmed in the replication population (p-value = 0.0007 and p-value = 0.018 respectively). We demonstrated for the first time one SNP on TREM-1, affecting its expression levels. These novel results, support the hypothesis that TREM-1 affects monocytes extravasation and accumulation processes leading to atherogenesis and atherosclerotic plaque progression, possibly through increased inflammation and subsequent higher expression of sL-selectin.
Highlights
Atherosclerosis is a multifactorial disease affecting arterial blood vessels due to a chronic inflammatory response
We investigated whether single nucleotide polymorphisms (SNPs) within or near the Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) gene were associated with soluble TREM-1 serum levels and with the expression levels of two TREM-1 splicing isoforms, more precisely, the membrane form and the soluble form (TREM-1sv)
HuGE navigator and NCBI dbSNP database searches resulted to the selection of 10 SNPs located within or near TREM-1 with a minor allele frequency >5%
Summary
Atherosclerosis is a multifactorial disease affecting arterial blood vessels due to a chronic inflammatory response. One of the early stages of atherosclerosis is the endothelial adhesion/ infiltration of white blood cells to the arterial sites, attracted by different pro-inflammatory molecules [1, 2]. This accumulative process gradually promotes inflammation and, by doing so, accelerates the atherosclerotic progression. The specific roles of these authors are articulated in the “author contributions” section. Our commercial affiliation did not play any funding role in our study
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