Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients

Abstract

Background and Objective Coronary artery disease (CAD) is a major cause of death worldwide. Revascularization via stent placement or coronary artery bypass grafting (CABG) are standard treatments for CAD. Despite a high success rate, these approaches are associated with long-term failure due to restenosis. Risk factors associated with restenosis were investigated using a case-control association study design. Methods Five thousand two hundred and forty-two patients were enrolled in this study and were assigned as follows: Stenosis Group: 3570 patients with CAD >50% without a prior stent or CABG (1394 genotyped), and Restenosis Group: 1672 patients with CAD >50% and prior stent deployment or CABG (705 genotyped). Binomial regression models were applied to investigate the association of restenosis with diabetes, hypertension, and dyslipidemia. The genetic association with restenosis was conducted using PLINK 1.9. Results Dyslipidemia is a major risk factor (Odds Ratio (OR) = 2.14, P-value <0.0001) for restenosis particularly among men (OR = 2.32, P < 0.0001), while type 2 diabetes (T2D) was associated with an increased risk of restenosis in women (OR = 1.36, P = 0.01). The rs9349379 ( PHACTR1) and rs264 ( LPL ) were associated with an increased risk of restenosis in our patients. PHACTR1 variant was associated with increased risk of restenosis mainly in women and in diabetic patients, while the LPL variant was associated with increased risk of restenosis in men. Conclusion The rs9349379 in PHACTR1 gene is significantly associated with restenosis, this association is more pronounced in women and in diabetic patients. The rs264 in LPL gene was associated with increased risk of restenosis in male patients.

HDL levels modulate the impact of type 2 diabetes susceptibility alleles in older adults

“…The gender distribution was as follows: for T2D, 39.2% were female and 60.8% were male; among those without T2D aged ≥ 60 years, 38.6% were female and 61.4% were male; in the ≥ 65 years group without T2D, 39.9% were female and 60.1% were male; and among those aged ≥ 70 years without T2D, 40.7% were female and 59.3% were male. The subjects are within the FGENTCARD, which is curruntly within the CARDIoGRAMplusC4D consortium [ 3 , 31 , 32 ]. The Lebanese American University Institutional Review Board’s ethics committee approved the study.…”