Nearly 1 in 5 With High Cholesterol in Community Sample Show Genetic Cause

In a community-based cohort of adults with primary high cholesterol, or hypercholesterolemia, the overall presence of an identifiable genetic cause was 17%, according to a study presented at the Scientific Sessions 2018 in Chicago, Illinois.

“Prior reports of the genetic etiology of hypercholesterolemia are affected by referral bias, inclusion of individuals with secondary hypercholesterolemia, and variability in identifying pathogenic variants,” researchers from the Mayo Clinic explained in the study abstract. “We sought to assess the prevalence of monogenic and polygenic etiologies in a community-based cohort of adults with primary hypercholesterolemia ([low-density lipoprotein cholesterol] LDL-C ≥155 mg/dL after excluding secondary causes).”

Researchers considered familial hypercholesterolemia present when Dutch Lipid Clinic Network (DLCN) scores were 6 or higher. DLCN scores between 3 and 5 indicated possible familial hypercholesterolemia. Participants underwent sequencing of familial hypercholesterolemia genes (LDLR, APOB, PCSK9) and genotyping of 12 single-nucleotide polymorphisms with known LDL-C association.

A pathogenic variant in LDLR, APOB, or PCSK9 was present in 1.3% of adults in the study, researchers reported. Polygenic etiology was present in 15.4%. Meanwhile, 0.2% had both a monogenic and polygenic etiology.

The overall prevalence of definite familial hypercholesterolemia in the study population was 0.9%; probable familial hypercholesterolemia, 6.1%; and possible familial hypercholesterolemia, 30%.

Among adults with definite familial hypercholesterolemia, a monogenic etiology was present in 2.4% and a polygenic etiology in 19.1%, according to the abstract. Among adults with probable familial hypercholesterolemia, a monogenic etiology was present in 9.5% and a polygenic etiology in 21%. And among those with possible familial hypercholesterolemia, a monogenic etiology was present in 26.7% and a polygenic etiology in 13.3%.

Just over half of participants with a monogenic etiology and 9.7% of participants with a polygenic etiology met criteria for familiar hypercholesterolemia. —Jolynn Tumolo