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Objective: To assess the effect of different ABO blood group gene locus on severity and prognosis of acute myocardial infarction (AMI). Methods: 100 patients with AMI diagnosed in our hospital from June 2018 to June 2019 were selected as the myocardial infarction group. At the same time, 100 healthy patients with physical examination results in our hospital were selected as the control group. Single-nucleotide polymorphisms of peripheral blood ABO gene loci rs505922, rs579459, rs643434, rs651007, and rs8176743 were detected. The differences of ABO blood group gene loci in different groups were compared. The correlation between the distribution of ABO blood group gene loci and the incidence and prognosis of patients with AMI was analyzed. Results: 98 cases were included in the myocardial infarction group and 99 cases were included in the control group. Compared with the control group, the genotypes of rs643434 and rs651007 locus in the myocardial infarction group were statistically significant (P<0.05). Analysis under different genetic models , compared with the control group, the myocardial infarction group had a significant difference in the rs643434 gene dominant mode, rs651007 dominant mode and recessive mode (P<0.05). The dominant mode of rs643434 was correlated with Gensini score and TIMI grade. The dominant mode of rs651007 was correlated with Gensini score, TIMI grade and troponin.The recessive mode of rs651007 was correlated with Gensini score, and the differences were statistically significant (P < 0.05). The dominant mode of rs643434 was related to the occurrence of MACE, and the difference was statistically significant (P < 0.05).Conclusion: Different genetic models of ABO blood group genes rs643434 and rs651007 may be related to the condition and prognosis of AMI.