The participation of ubiquitin-conjugating enzyme E2Z (UBE2Z) in atherosclerosis has been reported. We aimed to evaluate the association of the rs46522 polymorphism of the gene with myocardial infarction (MI) and other clinical and metabolic components in the Mexican population. A total of 2128 individuals (1023 patients with MI and 1105 healthy controls) were included. rs46522 was genotyped using the 5′ exonuclease TaqMan genotyping assay. A similar polymorphism distribution was observed between patients and healthy controls. The association between rs46522 polymorphism and cardiometabolic parameters was evaluated separately in the two groups. In the control group, rs46522 polymorphism was associated with increased risk of developing low-density lipoprotein cholesterol ≥130 mg/dL (odds ratio [OR] = 1.249, = 0.018; OR = 1.479, = 0.015; OR = 1.589, = 0.013). On the other hand, in MI patients, it was observed that rs46522 polymorphism was associated with an increased risk of developing high levels of alanine transaminase (OR = 1.297, = 0.043) and aspartate transaminase (OR = 1.453, = 0.009; OR = 1.592, = 0.001; OR = 1.632, = 0.001). Our results suggest that the gene rs46522 polymorphism is associated with abnormal metabolic parameters in Mexican patients with MI.