Association of TLR and TREM-1 gene polymorphisms with atherosclerosis severity in a Russian population

Abstract

Local vascular immune response is primarily initiated via Toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells-1 (TREM-1). We previously showed that certain TLR and TREM-1 gene polymorphisms are associated with coronary artery disease (CAD). Therefore, we hypothesized that these gene polymorphisms are associated with atherosclerosis severity. This study included 292 consecutive patients with CAD who were admitted to the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation) during 2011–2012. Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. We found that C/C genotype of the rs3804099 polymorphism within TLR2 gene and T/T genotype of the rs4711668 polymorphism within TREM-1 gene were significantly associated with severe coronary atherosclerosis while C allele of the rs5743551 polymorphism within TLR1 gene, A/G genotype of the rs4986790 polymorphism and C/T genotype of the rs4986791 polymorphism within TLR4 gene, and C allele of the rs3775073 polymorphism within TLR6 gene were significantly associated with severe noncoronary atherosclerosis. However, A/A genotype of the rs5743810 polymorphism within TLR6 gene was significantly associated with mild noncoronary atherosclerosis. We conclude that certain TLR and TREM-1 gene polymorphisms are significantly associated with atherosclerosis severity in a Russian population.

Prognostic Utility of Soluble TREM‐1 in Predicting Mortality and Cardiovascular Events in Patients With Acute Myocardial Infarction

“…Recently, studies reported that TREM‐1 contributes to the development of atherosclerosis through promoting monocytosis, monocyte/macrophage proinflammatory responses, and formation of inflammatory foam cells 23, 24. TREM‐1 gene polymorphisms are significantly associated with higher coronary atherosclerosis severity in a Russian population 25. Moreover, TREM‐1 mediates inflammatory injury and cardiac remodeling after myocardial infarction in mice and pigs 8…”

The role of gene TREM-1 at children who have operation congenital heart diseases

“…Недавние исследования демонстрируют роль гена TREM-1 в патогенезе и лечении сердечно-сосудистых заболеваний [7], в частности атеросклероза [8], инфекционного эндокардита [9] и некоторых других [10]. Помимо этого, в ряде работ установлены ассоциативные связи полиморфных вариантов гена TREM-1 с предрасположенностью к развитию неонатальной смертности [11], болезни Альцгеймера [12], а также часть исследований направлена на изучение септических заболеваний [13].…”

TREM-1; is It a Pivotal Target for Cardiovascular Diseases?

“…TREM-1 was also found to amplify the inflammation following myocardial infraction and its modulation provides better outcome for post AMI in both short and long term 15 . Studies endeavored to find any polymorphism in TREM-1 gene expression associated with atherosclerosis remains elusive on their conclusion, however, it has been found that sTREM-1 is increased in AMI is associated with SNP polymorphism 61,62 ). Elevated levels of serum sTREM-1 is associated with incidence of in stent-restenosis (ISR) and also TREM-1 expression is seen more in the VSCMs of the neointimal and medial region of the stenotic artery, TREM-1 inhibition could play a modulating role in this phenomenon 63,64 .…”