Association of the PCSK6 rs1531817(C/A) polymorphism with the prognosis and coronary stenosis in premature myocardial infarction patients: a prospective cohort study

TL;DR

This study finds that a specific PCSK6 gene variant is linked to less severe heart artery blockage and better outcomes in young heart attack patients.

Contribution

The study identifies a protective PCSK6 rs1531817 genotype against coronary stenosis and adverse outcomes in premature myocardial infarction patients.

Findings

The PCSK6 rs1531817 CA+AA genotype is an independent protective factor against high Gensini score and triple vessel disease.

The same genotype is associated with lower risk of major adverse cardiovascular events.

ApoA1/ApoB and TC/HDL partially mediate the protective effects of the PCSK6 polymorphism.

Abstract

Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients.

This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs.

92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs.

Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.

The online version contains supplementary material available at 10.1186/s12944-024-02206-w.

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