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PLoS One. 2017 Aug 3;12(8):e0182226. doi: 10.1371/journal.pone.0182226. eCollection 2017.

TREM-1 SNP rs2234246 regulates TREM-1 protein and mRNA levels and is associated with plasma levels of L-selectin.

Author information

1
UMR INSERM U1122; IGE-PCV 'Interactions Gène-Environnement en Physiopathologie Cardiovasculaire', Faculté de Pharmacie-Université de Lorraine, Nancy, France.
2
INOTREM, Nancy, France.
3
Réanimation Médicale, Hôpital Central, Nancy, France.
4
Department of Internal Medicine and Geriatrics, CHU Technopôle Nancy-Brabois, Rue du Morvan, Vandoeuvre-lès-Nancy, France.

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.

PMID:
28771614
PMCID:
PMC5542552
DOI:
10.1371/journal.pone.0182226
[Indexed for MEDLINE]
Free PMC Article

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