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TREML4 polymorphisms increase the mRNA in blood leukocytes in the progression of atherosclerosis
Victor Hugo Rezende Duarte1, Marina Sampaio Cruz2, Adriana Bertolami3
1Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, S/N, Natal, Rio Grande do Norte, 59012-570, Brazil. victorhugorezendeduarte@gmail.com.
Insights
Triggering receptor expressed in myeloid cell 4 (TREML4) gene variants influence its expression in leukocytes. Minor alleles of TREML4 polymorphisms rs2803495 and rs280396 are linked to altered TREML4 mRNA levels, but not early atherosclerosis or post-myocardial infarction stages.
Area of Science:
- Immunology
- Genetics
- Cardiovascular Medicine
Background:
- Members of the triggering receptor expressed in myeloid cell (TREM) family, including TREML4, are implicated in atherosclerosis risk and progression.
- Existing research suggests associations between TREM family members and coronary artery disease, acute coronary syndrome, and coronary artery calcification.
Purpose of the Study:
- To investigate the relationship between TREML4 gene expression, its polymorphisms (rs2803495 and rs280396), and subclinical atherosclerosis or heart failure post-myocardial infarction (MI).
- This study is the first to examine TREML4 variants and expression in these specific patient cohorts.
Main Methods:
- Analysis of TREML4 variants (rs2803495 A>G and rs280396 T>C) and leukocyte mRNA expression using quantitative reverse transcription PCR (qRT-PCR).
- Study population included patients with subclinical atherosclerosis (n=340) and heart failure post-MI (n=68).
Main Results:
- The G allele of rs2803495 was significantly associated with TREML4 expression (OR 8.01, p<0.001).
- Patients with the C minor allele of rs280396 (TC/CC genotypes) showed higher TREML4 expression compared to those without the C allele (OR 10.42, p<0.001 for likelihood; OR 4.88, p<0.001 for expression levels).
- TREML4 was not associated with early atherosclerotic plaque formation or later stages post-MI.
Conclusions:
- TREML4 mRNA expression in blood leukocytes is influenced by minor alleles of polymorphisms rs2803495 and rs280396.
- TREML4 expression may play a role in atherosclerosis progression, but not in asymptomatic disease or the post-MI phase.
Abstract:
TREML4 and other members of the triggering receptor expressed in the myeloid cell family are associated with a risk of atherosclerosis and progression in coronary artery disease, acute coronary syndrome, and coronary artery calcification. Herein, the relationship between TREML4 expression and its polymorphisms (rs2803495 and rs280396) was evaluated in patients with subclinical atherosclerosis (n = 340) and heart failure post-acute myocardial infarction (MI) (n = 68) for the first time. TREML4 variants rs2803495 (A > G) and rs2803496 (T > C) and leukocyte mRNA expression was analyzed by qRT-PCR. The rs2803495 G allele was associated with TREML4 expression (OR 8.01, CI 3.78-16.99, p < 0.001). Patients carrying the rs2803496 C minor allele (TC/CC genotypes) were more likely to express TREML4 than those without the C allele (OR 10.42, CI 4.76-22.78, p < 0.001), as well as having higher levels of TREML4 expression (OR 4.88, CI 2.35-10.12, p < 0.001). Thus, we report for the first time that TREML4 is not associated with the early stages of atherosclerotic plaque formation and later stages after MI. In conclusion, TREML4 mRNA expression in blood leukocytes is influenced by minor alleles (G and C) and may regulate differently during the atherosclerosis progression stages, but not in asymptomatic atherosclerosis disease and post-MI.
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