The Genetic Risk Score with Variants at PDGFs and PDGFRB for the Risk of Major Cardiovascular Adverse Events in Patients with Coronary Artery Disease

Abstract

Background Previous studies linked platelet-derived growth factors (PDGFs) and its receptor beta (PDGFRB) genetic variants to coronary artery disease (CAD), but their impact on major adverse cardiovascular events (MACEs) remains unclear. Methods A cohort study of 3139 CAD patients, followed until December 1, 2022 (median 5.42 years), genotyped 13 tagSNPs in PDGFs/PDGFRB pathway genes to establish weighted genetic risk scores (wGRS). Adjusted Cox regression analyzed the association of SNPs and wGRS with MACE outcomes. The wGRS impact on traditional risk factors (TRFs) and Global Registry of Acute Coronary Events (GRACE) score for MACEs was assessed using the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Multiple Cox regression examined coronary artery lesion counts and MACE occurrence in wGRS groups. Results The results showed that the A allele (vs G allele) of rs246390 was associated with an increased risk of MACEs (adjusted HR = 1.171, P = 0.013) and CVD (adjusted HR = 1.174, P = 0.036). Compared to low wGRS_MACE (Q1 of quintile), high wGRS_MACE (Q5 of quintile) had an increased risk of MACEs with adjusted HRs of 1.441 (P = 0.006). Additionally, patients with vessel lesions in medium wGRS_CVD (Q2 ~ Q4) and high wGRS_CVD (Q5) groups showed significantly higher CVD incidence than those with no vessel lesion and low wGRS_CVD (Q1) levels, with adjusted HRs of 2.427 and 2.724 (P < 0.001) respectively. Conclusions Variants of the PDGF-PDGFRB pathway genes contribute to the risk of MACEs after CAD; the wGRS could serve as a risk predictor of MACEs in addition to TRFs.