Polygenic Hypercholesterolemia

Coronary heart disease and stroke are the two leading causes of death worldwide and by the year 2030, they are projected to account for nearly 25% of deaths. Association of hypercholesterolemia with these two conditions makes it a major contributor to the global disease burden and cardiovascular disease associated with mortality and morbidity. Hypercholesterolemia is a condition wherein the combination of genetic mutations and environmental factors like an excessive amount of fat in diet, obesity and physical inactivity lead to elevated serum cholesterol levels. Familial hypercholesterolemia is a condition where a mutation in genes LDLR, APOB, PCSK genes cause an elevation in levels of total cholesterol and LDL-C. Diagnosis of FH needs the following criteria - increased cholesterol levels, physical stigmata e.g tendon xanthomas or evidence of these signs in first or second-degree relatives and a family history of premature coronary artery disease. In approximately 60% the mutation is negative in the above-mentioned genes, leading to a polygenic cause of hypercholesterolemia. Hypercholesterolemia of genetic origin negative for mutations in LDLR, APOB, PCSK9 genes is Polygenic hypercholesterolemia. The mutation in several small LDL raising alleles ( single nucleotide polymorphism genes) leads to polygenic hypercholesterolemia which can be determined by genetic score. Familial hypercholesterolemia leads to early development of atherosclerotic cardiovascular disease which include coronary artery disease, transient ischemic attack, stroke, peripheral artery disease. The risk is lower in polygenic variety than monogenic type.