Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Monogenic, polygenic, and oligogenic familial hypercholesterolemia

Tada, Hayato; Nohara, Atsushi; Kawashiri, Masa-aki

doi: 10.1097/QCO.0000000000000563

Purpose of review Familial hypercholesterolemia has long been considered a monogenic disorder. However, recent advances in genetic analyses have revealed various forms of this disorder, including polygenic and oligogenic familial hypercholesterolemia. We review the current understanding of the genetic background of this disease.

Recent findings Mutations in multiple alleles responsible for low-density lipoprotein regulation could contribute to the development of familial hypercholesterolemia, especially among patients with mutation-negative familial hypercholesterolemia. In oligogenic familial hypercholesterolemia, multiple rare genetic variations contributed to more severe familial hypercholesterolemia.

Summary Familial hypercholesterolemia is a relatively common ‘genetic’ disorder associated with an extremely high risk of developing coronary artery disease. In addition to monogenic familial hypercholesterolemia, different types of familial hypercholesterolemia, including polygenic and oligogenic familial hypercholesterolemia, exist and have varying degrees of severity. Clinical and genetic assessments for familial hypercholesterolemia and clinical risk stratifications should be performed for accurate diagnosis, as should cascade screening and risk stratification for the offspring of affected patients.

Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

Correspondence to Hayato Tada, MD, Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, 920-8641, Japan. Tel: +81 76 265 2000 2251; fax: +81 76 234 4251; e-mail:

All authors contributed to manuscript preparation.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.