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TREML4 多态性增加了动脉粥样硬化进展过程中血液白细胞中的 mRNA。

TREML4 polymorphisms increase the mRNA in blood leukocytes in the progression of atherosclerosis.

机构信息

Department 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.

Dyslipidemia Medical Section, Dante Pazzanese Institute of Cardiology, Av. Dr. Dante Pazzanese, 500, São Paulo, 04012-909, Brazil.

出版信息

Sci Rep. 2022 Nov 3;12(1):18612. doi: 10.1038/s41598-022-22040-3.

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.

摘要

TREML4 和其他髓系细胞表达的触发受体家族成员与动脉粥样硬化风险以及冠状动脉疾病、急性冠状动脉综合征和冠状动脉钙化的进展相关。在此,首次评估了无症状动脉粥样硬化(n=340)和急性心肌梗死后心力衰竭(n=68)患者中 TREML4 表达及其多态性(rs2803495 和 rs280396)之间的关系。通过 qRT-PCR 分析了 TREML4 变体 rs2803495(A>G)和 rs2803496(T>C)和白细胞 mRNA 表达。rs2803495 G 等位基因与 TREML4 表达相关(OR 8.01,95%CI 3.78-16.99,p<0.001)。携带 rs2803496 C 次要等位基因(TC/CC 基因型)的患者比不携带 C 等位基因的患者更有可能表达 TREML4(OR 10.42,95%CI 4.76-22.78,p<0.001),并且 TREML4 表达水平更高(OR 4.88,95%CI 2.35-10.12,p<0.001)。因此,我们首次报道 TREML4 与动脉粥样硬化斑块形成的早期阶段和 MI 后晚期无关。总之,血液白细胞中 TREML4 mRNA 的表达受次要等位基因(G 和 C)的影响,并且在动脉粥样硬化进展阶段可能以不同的方式调节,但在无症状动脉粥样硬化疾病和 MI 后不会调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9633690/bc4d88d58c63/41598_2022_22040_Fig1_HTML.jpg

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