PCSK9 gene variations in the clinical setting of premature cardiovascular disease: A critical appraisal

Information about PCSK9 gene variations and its association with cardiovascular (CV) disease is controversial. We aimed to evaluate 3 reported polymorphisms in PSCK9 in a cohort of young patients with myocardial infarction with ST segment elevation (STEMI). Retrospective study of consecutive patients with premature STEMI (2018–2023). 216 patients with STEMI due atherothrombotic coronary artery disease (CAD), confirmed by coronary angiogram, were included. We genotyped 3 polymorphisms in PCSK9 (rs12117661, rs2483205, rs505151) in 207 patients (DNA unavailable in 9) and a control group (N = 200). Mean age 49.4 ± 6,6 years (82.4% men). Genotypes frequencies distribution in patient's and control's cohorts did not deviate from the expected by Hardy-Weinberg equilibrium and there were no significant differences between patients and controls. Among patients, we did not find any association between PSCK9 genotypes and clinical variables (gender, age, CV risk factors, cholesterol levels, family history of premature CAD or number of coronary arteries affected). We did not find any association between PSCK9 genotypes (RS12117661, RS2483205 and RS505151) and any CV risk factors or the extent of CAD in a cohort of patients with premature STEMI. There were not differences in the genotype distribution between patients and controls. •Pathogenic variants in PCSK9 cause of autosomal dominant familial hypercholesterolemia. According to genetic information, clinicians can follow specific clinical guidelines familial hypercholesterolemia, and provide preventive strategies for all carriers in the family. Familial genetic screening is recommended.•Available information about PCSK9 gene variations (polymorphisms) and its association with an increased risk of cardiovascular (CV) disease is controversial. Critical interpretation of these finding is imperative before trying to translate anything into clinical practice.•In this study, we evaluated 3 reported polymorphisms in PSCK9 (rs12117661, rs2483205, rs505151). In our cohort of young patients with myocardial infarction with ST segment elevation, we did not find any association with CV disease. Therefore, we do not believe that its analyses should be translated to clinical practice.