Familial hypercholesterolemia: is it time to separate monogenic from polygenic familial hypercholesterolemia?

摘要

Purpose of review This review explores the concepts of monogenic and the so-called polygenic familial hypercholesterolemia and how the identification of familial hypercholesterolemia as a monogenic condition and its separation from polygenic primary hypercholesterolemia may have implications for clinical practice. Recent findings Through genetic testing, a mutation in any of the three known autosomal dominant familial hypercholesterolemia-causing genes is found in 60-80% of cases with a clinical diagnosis of definite familial hypercholesterolemia. As individuals with a polygenic basis for their hypercholesterolemia do not follow the same inheritance pattern observed in monogenic familial hypercholesterolemia, the use of family-based cascade screening in individuals with a polygenic origin is not recommend, as only 30% of relatives have an elevated LDL-C compared to the 50% in monogenic families. The presence of a causative monogenic mutation associates the highest cardiovascular risk vs. not having a mutation or having a polygenic background, providing prognostic information independent of LDL-C. It may also help assess intensity of interventions. Treatment adherence also seems to be higher after monogenic confirmation of hypercholesterolemia. Knowledge about the genetic status of an individual with clinical familial hypercholesterolemia (monogenic vs. polygenic) can provide a more informed understanding to evaluating risk, managing disease and opportunities for screening strategies.