Chang Jianshe, Shao Rui, Xu Xiangshan, Jin Yuanzhe
Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Key Laboratory of Liaoning Provincial Medicine and Engineering of Cardiovascular Fluid Dynamics, China Medical University, Shenyang, China.
Front Cardiovasc Med. 2024 Sep 20;11:1442098. doi: 10.3389/fcvm.2024.1442098. eCollection 2024.
This study aims to explore the association of methyltransferase-like protein 3 (METTL3) expression with severity of coronary artery stenosis in patients with coronary heart disease (CHD).
A total of 100 patients administrated in the Fourth Affiliated Hospital of China Medical University between October 2022 and June 2023 with primary symptoms of chest pain or tightness, or cardiac discomfort, and who underwent coronary angiography for a definitive diagnosis, were included in the study. The baseline characteristics, including TG, TC, LDL-C, HDL-C, uric acid and past history were recorded. Peripheral blood samples were collected to assess the expression levels of METTL3, YT521-B homology domains 1 (YTHDF1), YT521-B homology domains 2 (YTHDF2), and YT521-B homology domains 3 (YTHDF3) using the PCR method. Relative expression levels of METTL3 protein were determined by Western blotting. Correlation analysis were conducted to evaluate the relationship between METTL3/YTHDF1 gene expression and clinical data. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of METTL3 and YTHDF1 for CHD. Binary logistic regression was used to determine whether the expression of METTL3 and YTHDF1 in peripheral blood were risk factors for CHD.
The study found no significant differences in baseline characteristics between CHD patients and controls, except for length of stay, Lymphocytes, Neutrophils, AST, HDL-C and modified Gensini score. The gene expression levels of METTL3 and YTHDF1 were significantly higher in CHD patients compared to controls ( < 0.05). Furthermore, METTL3 protein expression was also significantly elevated in the CHD group compared to the control group ( < 0.05). METTL3 gene expression correlated with HDL-C and Gensini score, while YTHDF1 gene expression correlated with Age, WBC, Neutrophils, RDW-CV, modified Gensini score. ROC curve analysis demonstrated an AUC of 0.692 for METTL3 in CHD, with a sensitivity of 66.7% and a specificity of 69.8% at a cut-off value of >0.052. The AUC for YTHDF1 in CHD was 0.623, with a sensitivity of 47.4% and a specificity of 74.4% at a cut-off value of >0.027. Binary logistic regression revealed that only increased METTL3 expression in peripheral blood was an independent risk factor for CHD ( < 0.05).
The increased expression of METTL3 in peripheral blood may serve as a potential biomarker and predictive factor for CHD.
本研究旨在探讨甲基转移酶样蛋白3（METTL3）表达与冠心病（CHD）患者冠状动脉狭窄严重程度之间的关联。
纳入2022年10月至2023年6月在中国医科大学附属第四医院就诊的100例以胸痛或胸闷、心脏不适为主诉且接受冠状动脉造影以明确诊断的患者。记录基线特征，包括甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、尿酸及既往史。采集外周血样本，采用聚合酶链反应（PCR）法评估METTL3、YT521-B同源结构域1（YTHDF1）、YT521-B同源结构域2（YTHDF2）和YT521-B同源结构域3（YTHDF3）的表达水平。通过蛋白质免疫印迹法测定METTL3蛋白的相对表达水平。进行相关性分析以评估METTL3/YTHDF1基因表达与临床数据之间的关系。采用受试者工作特征（ROC）曲线分析评估METTL3和YTHDF1对冠心病的预测价值。采用二元逻辑回归确定外周血中METTL3和YTHDF1的表达是否为冠心病的危险因素。
研究发现，除住院时间、淋巴细胞、中性粒细胞、谷草转氨酶（AST）、HDL-C和改良Gensini评分外，冠心病患者与对照组的基线特征无显著差异。与对照组相比，冠心病患者中METTL3和YTHDF1的基因表达水平显著更高（<0.05）。此外，与对照组相比，冠心病组中METTL3蛋白表达也显著升高（<0.05）。METTL3基因表达与HDL-C和Gensini评分相关，而YTHDF1基因表达与年龄、白细胞（WBC）、中性粒细胞、红细胞分布宽度变异系数（RDW-CV）、改良Gensini评分相关。ROC曲线分析显示，冠心病中METTL3的曲线下面积（AUC）为0.692，在临界值>0.052时，灵敏度为66.7%，特异性为69.8%。冠心病中YTHDF1的AUC为0.623，在临界值>0.027时，灵敏度为47.4%，特异性为74.4%。二元逻辑回归显示，仅外周血中METTL3表达增加是冠心病的独立危险因素（<0.05）。
外周血中METTL3表达增加可能是冠心病的潜在生物标志物和预测因素。
