Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2) is known for its anti-inflammatory properties during the immune response, and influences negatively on TNF-α expression levels. Genetic epidemiology studies have identified polymorphisms located in the TREM2 gene associated with neurodegenerative and chronic inflammatory diseases. TREM2 levels have been observed to affect plasma levels of TNF-α and plaque stability in symptomatic and asymptomatic patients with carotid stenosis. In this study, we investigated polymorphisms located in the TREM2 gene region and association with TNF-α levels and the intima media thickness of the femoral artery. The discovery population from the STANISLAS Family Study comprised of 809 individuals, whereas the replication population utilized an independent cohort of French origin (n = 916). Our results suggest that the minor allele (T) of SNP rs6918289 is positively associated with elevated plasma levels of TNF-α in discovery and replication populations (P = 0.0026, SE = 0.04 and P = 0.023, SE = 0.09, respectively), including femoral artery thickness in the discovery cohort (P = 0.026, SE = 0.009). Results indicate that rs6918289 may be considered as a risk factor for inflammatory diseases and could be used in stratified medicine with patients diagnosed with chronic inflammatory-related conditions, such as atherosclerosis.
Highlights
The triggering receptors expressed on myeloid cells (TREM) family molecules are members of the immunoglobulin superfamily of receptors
No genetic determinants have been identified in the Triggering receptor expressed on myeloid cells 2 (TREM2) locus affecting plasma levels of TNF-α and/or intima media thickness
We have studied the association of variants located in the TREM2 gene regionwith plasma levels of TNF-α and intima media thickness of the femoral artery (IMT-F)
Summary
The triggering receptors expressed on myeloid cells (TREM) family molecules are members of the immunoglobulin superfamily of receptors. All five genes from the TREM family (Table 1) are situated in the 6p21.1 region of the chromosome[1] and mediate signaling in immune cells, playing critical roles in inflammatory responses[2]. TREM2 portrays anti-inflammatory properties during the immune response[6,7], including: stimulation of phagocytosis and suppression of cytokine production, e.g. TNF-α8,9, one of the most important molecules for the regulation of inflammation, and reflects the degree of inflammatory response. It is evident that TREM2 acts as a protective molecule in chronic inflammatory diseases. Studies in transgenic mice have demonstrated that deficiency of TREM2 protein may accelerate the aging process, reduce microglial activity and result in neuroinflammation, which plays a major role in all neurodegenerative diseases[10]. No genetic determinants have been identified in the TREM2 locus affecting plasma levels of TNF-α and/or intima media thickness
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