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BACKGROUND To analyze the expression levels of plasma dimethylglycine (DMG), human maternally expressed gene 3 (MEG3), and Apelin-12 in patients with acute myocardial infarction (AMI) and explore their clinical significance. METHODS One hundred and ten patients with suspected AMI (chest pain duration <6 h) who were admitted to our hospital between December 2018 and June 2020 were included. Plasma DMG, MEG3, and Apelin-12 levels were measured at the time of admission. The levels of plasma DMG, MEG3, and Apelin-12, as well as the general data and admission baseline data of these patients were then compared with those of non-AMI patients. The receiver operating characteristic (ROC) curve was used to analyze the clinical value of plasma DMG, MEG3, and Apelin-12 levels for the early diagnosis of AMI. RESULTS Among the 110 patients with chest pain suspected of AMI, 34 were clinically diagnosed with AMI, and 76 were non-AMI patients. The proportion of males, smoking, history of myocardial infarction, and congestive heart failure in the AMI group were higher than those of the non-AMI group. The proportions of systolic blood pressure (SBP), ST-segment elevation, and electrocardiogram (ECG) dynamic changes on admission were also higher in the AMI group compared to those of the non-AMI group (P<0.05). The plasma DMG, MEG3, and Apelin-12 levels of patients in the AMI group on admission were higher than those of the non-AMI group (P<0.05); all have diagnostic value for AMI upon admission. The area under the curve (AUC) of MEG3 was higher than that of both DMG and Apelin-12, however the difference was not statistically significant (Z=1.378, 0.934, P=0.168, 0.350). Using 0.015 as the cut-off value for MEG3-messenger ribonucleic acid (mRNA), the sensitivity and specificity for diagnosing AMI were 85.29% and 81.58%, respectively. CONCLUSIONS Our results showed that the plasma levels of DMG, MEG3, and Apelin-12 in patients with AMI were high, and thus, they can be used as biomarkers for the early diagnosis of AMI. Among them, MEG3 was the most effective in early diagnosing AMI.