Familial hyperlipidemia caused by Apolipoprotein B mutation in the Pediatric Amish population: A mini review

Corey Snyder, Amber L. Beitelshees, Devyani Chowdhury

Familial Hypercholesterolemia (FH) is an autosomal dominant genetic disorder that causes increased low density lipoprotein cholesterol (LDL-C) levels and a higher risk of premature atherosclerosis and cardiovascular disease (CVD). Common causes of FH include inherited genetic mutations in the LDLR, APOB, and PCSK9 genes. LDLR, APOB, and PCSK9 mutations account for 79%, 5%, and <1% of cases of FH respectively. Apolipoprotein B (ApoB) is the necessary atherogenic lipoprotein which can serve as a determinant of cardiovascular disease including hypercholesterolemia. A founder variant in Apolipoprotein B (APOB p.R3527Q) causes FH and is found in 12% of the Pennsylvania Amish population. This article provides an overview of ApoB metabolism and clinical manifestations associated with APOB mutations. An understanding of the clinical manifestations caused by APOB p.R3527Q can be beneficial for the clinical diagnosis and treatment of FH in the Amish. Based on previous studies, changes in LDL cholesterol (LDL-C), LDL particles (LDL-P), small dense LDL particles, and ApoB levels can be seen among these patients putting them at an increased risk for atherosclerotic issues, vascular hardening, and changes in endothelial function, particularly among homozygous individuals.