Analysis of Genetic Variants of ANGPTL4 Gene Responsible for Atherosclerosis Severity in Cardiac Patients

ANGPTL4 gene is a major factor in the onset of atherosclerosis and exacerbation of its severity. ANGPTL4 regulates lipoprotein lipase (LPL), but its inhibitory effect causes decreased triglyceride clearance. The E40K mutation reduces ANGPTL4 oligomer formation, reducing LPL activity suppression. Objectives: To correlate ANGPTL4 N-terminal chain variations with atherosclerotic cardiovascular disease severity in Pakistani individuals, enabling diagnosis, treatment, and prevention. Methods: A case control study was conducted at Surgimed Hospital, Lahore on 100 Pakistani cardiovascular patients and 50 healthy control subjects. The N-terminal chain of the ANGPTL4 gene was sequenced revealing 14 individuals (9.33%) were heterozygous carriers of the ANGPTL4 gene variant (rs116843064; G>A, E40K) in our population (n=150). Results: Among the participants, four (2.67%) individuals had severe atherosclerosis with heterozygous genotype (GA), eight (5.33%) had mild atherosclerosis with heterozygous genotype (GA), and two were healthy controls (1.33%) with heterozygous genotype (GA). This study showed the significant association of E40K variant of N-terminal chain of ANGPTL4 with less likely chance of severe atherosclerosis in our cardiovascular patients. The E40K alters the regulation of lipoprotein lipase, affecting lipid levels and impacting cardiovascular health. Conclusions: E40K mutation carriers exhibit a lower risk of severe atherosclerosis in cardiovascular patients due to better lipid profiles as HDL levels were lower in non-carriers and higher in carriers.