Effect of circadian rhythm gene Period2 rs934945 gene polymorphism on long-term prognosis of patients with early onset acute myocardial infarction after PPCI: a prospective cohort study

Abstract Background Disruption of endogenous circadian rhythms increases the risk of myocardial infarction. A few studies have confirmed that polymorphisms in the circadian rhythm gene PER2 are closely related to the onset of acute myocardial infarction (AMI), but there are few reports on its correlation with the prognosis of AMI patients. Purpose This study explores the impact of the single nucleotide polymorphism site rs934945 of the PER2 gene on the occurrence of major adverse cardiovascular events (MACE) in patients with premature acute myocardial infarction (PMI) in the long term. Methods A total of 640 patients with PMI who underwent emergency percutaneous coronary intervention (PPCI) from January 2017 to August 2022 were consecutively included. Male were ≤ 50 years and female were ≤ 55 years . The PER2 rs934945 gene polymorphism was analyzed by MassARRAY nucleic acid mass spectrometry analysis system. The onset time was divided into four time periods (00:00-05:59, 06:00-11:59, 12:00-17:59, 18:00-23:59). Follow-up time was 5 years, and MACE events were recorded. COX regression analysis was used to analyze association between gene polymorphism and MACE , as well as multivariate subgroup analysis and interaction. Results 353 have CC genotype, 234 have CT genotype, and 53 have TT genotype. The frequencies of C allele (wild type) and T allele (mutant type) were 0.734 and 0.266 respectively, which were different from those in other regions. Patients with CT + TT genotype who developed disease was higher than with CC genotype during 00:00-05:59 period (25.80% vs 17.80%), and the difference was statistically significant (Z =5.927, P 0.05). The levels of Lp(a) and hs-CRP in CT + TT group were higher than in CC group (P 0.05). Compared with CC genotype, overall risk of MACE in PMI patients with CT + TT genotype increased by 119% (HR 2.19, 95% CI: 1.73, 15.16, P = 0.01), and risk ratio was the highest in subgroup with high-sensitivity troponin T 2.93, which was 5.34 (95% CI 1.67, 17.10, P = 0.005). In the interaction analysis, there was no interaction between genotype and onset time for MACE, with risk ratio of 0.985 (95% CI: 0.92, 1.05, P 0.05). There was an interaction between genotype and high-sensitivity troponin T for MACE. Compared with CC genotype and high-sensitivity troponin T ≤ 2.93, the risk of MACE in patients with CT + TT genotype and high-sensitivity troponin T 2.93 increased significantly to 6.38 times (95% CI: 2.14, 18.96, P 0.05). Conclusion PMI onset in the 00:00-05:59 period was high in the PER2 rs934945 CT+TT genotype group. The genotype was correlated with risk prediction of long-term MACE , and the interaction with high-sensitivity troponin T significantly increased risk of MACE.