Genetic Profile of Premature Coronary Artery Disease Associated With Dyslipidemia: A Preliminary Study in Tertiary Hospitals.

Abstract

Background Familial Hypercholesteolemia (FH) represents significant risk for premature Coronary Artery Disease (CAD) development. Testing for causative mutations is the gold standard diagnostic test for FH. This study aimed to estimate the prevalence of genetically-confirmed Familial Hypercholesterolemia in premature Coronary Artery Disease patients in an Egyptian cohort. Methods: An Observational Analytical Cross-sectional study was conducted at Kobri Alqoba military hospital in Egypt in 2022, including 47 participants. All participants underwent Next generation sequencing for 7 genes linked with FH development in 47 patients with Premature CAD. Results: 9 Variants of Uncertain Significance (VUS) were found in LDLR, APOB, and APOE genes in 20 of 47 (42.5%) patients. Four variants; LDLR (rs141673997), APOB (rs772173177), APOB (rs41288783), and APOB (NM_000384.3) were novel. No pathogenic or likely pathogenic variants were detected. The prevalence of definite/probable FH diagnosed by DLCN criteria were 14.8% (7/47). DLCN criteria detected only 1 patient with a VUS (14.3%). Only three of the entire cohort had LDL levels <55 mg/dl, and none of the patients carrying a VUS had LDL level <55 mg/dl. Conclusions: DLCN scoring system is not an accurate screening tool for Familial Hypercholesterolemia and genetic testing for accurate diagnosis and management of FH is essential for high risk cases. FH is undertreated in Egypt and better control of dyslipidemia is warranted in patients with this condition.