Genetic and Secondary Causes of Severe HDL Deficiency and Cardiovascular Disease

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2018 Oct 19

PMID 30333156

Citations 20

Authors

Andrew S Geller

Eliana Y Polisecki

Margaret R Diffenderfer

Bela F Asztalos

Sotirios K Karathanasis

Robert A Hegele

Ernst J Schaefer

Affiliations

Soon will be listed here.

Abstract

We assessed secondary and genetic causes of severe HDL deficiency in 258,252 subjects, of whom 370 men (0.33%) and 144 women (0.099%) had HDL cholesterol levels <20 mg/dl. We excluded 206 subjects (40.1%) with significant elevations of triglycerides, C-reactive protein, glycosylated hemoglobin, myeloperoxidase, or liver enzymes and men receiving testosterone. We sequenced 23 lipid-related genes in 201 (65.3%) of 308 eligible subjects. Mutations (23 novel) and selected variants were found at the following gene loci: ) (26.9%): 2 homozygotes, 7 compound or double heterozygotes, 30 heterozygotes, and 2 homozygotes and 13 heterozygotes with variants rs9282541/p.R230C or rs111292742/c.-279C>G; ) (12.4%): 1 homozygote, 3 compound heterozygotes, 13 heterozygotes, and 8 heterozygotes with variant rs4986970/p.S232T; ) (5.0%): 1 homozygote and 9 heterozygotes; and ) (4.5%): 1 heterozygote and 8 heterozygotes with variant rs268/p.N318S. In addition, 4.5% had other mutations, and 46.8% had no mutations. Atherosclerotic cardiovascular disease (ASCVD) prevalence rates in the , , , , and mutation-negative groups were 37.0%, 4.0%, 40.0%, 11.1%, and 6.4%, respectively. Severe HDL deficiency is uncommon, with 40.1% having secondary causes and 48.8% of the subjects sequenced having , , , or mutations or variants, with the highest ASCVD prevalence rates being observed in the and groups.

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