Role of Hyperlipidemia-Related <i>PCSK9</i>, <i>APOE</i>, and <i>LRP8</i> Variants in Restenosis after Stent Implantation in Male Patients: A Case-Control Study

Abstract

Introduction: This study aimed to evaluate the contribution of hyperlipidemia-related genetic variants, including protein convertase subtilisin/kexin type 9 (PCSK9; rs374603772, rs67608943, rs2182833, rs11206510), apolipoprotein E (APOE) epsilon alleles, and low-density lipoprotein receptor-related protein 8 (LRP8, also known as APOE2R; rs5174) to restenosis susceptibility in male patients with coronary artery disease (CAD) following stent implantation. Methods: A case-control design was applied, including male patients who developed restenosis (R; n = 85) and those without restenosis after stenting (OS; n = 66). Genetic variants were analyzed using fluorescent end-point PCR, and genotype-phenotype associations were assessed in relation to metabolic and clinical parameters. Results: Compared with the OS group, patients in the R group exhibited higher LDL cholesterol levels, increased prevalence of hyperlipidemia, and lower HDL cholesterol levels (all p < 0.05). After correction for multiple comparisons, genotype analysis showed that the LRP8 rs5174 AA genotype was more prevalent in the R group (p = 0.009). No significant differences were observed for APOE epsilon, PCSK9 rs2182833, or rs11206510 genotypes. Notably, within the R group, the PCSK9 rs2182833 AA genotype was more frequently observed among nondiabetic and normolipidemic patients, indicating a possible association with a more favorable metabolic profile. Multivariate analysis identified hyperlipidemia and the LRP8 rs5174 AA genotype as independent risk factors for restenosis. Conclusion: These findings suggest LRP8 rs5174 polymorphism may act as a potential modifier for restenosis risk in male patients with CAD. Furthermore, the observed association between PCSK9 rs2182833 and metabolic traits appears suggestive and context-dependent. Collectively, the results underscore the potential contribution of these lipid-related genetic variations to restenosis susceptibility and highlight the need for validation in larger cohorts.