Related Experiment Video
Updated: Apr 20, 2026
Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Common low-density lipoprotein receptor p.G116S variant has a large effect on plasma low-density lipoprotein
Joseph B Dubé1, Jian Wang1, Henian Cao1
1From the Molecular Medicine Group, Robarts Research Institute (J.B.D., J.W., H.C., A.M., C.T.J., R.S., S.H., B.A.K., M.R.B., R.A.H.) and Department of Medicine (C.T.J., R.A.H.), Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada; The Center for Alaska Native Health Research, Institute of Arctic Biology, University of Alaska Fairbanks (S.E.H., B.B.B.); The Dalla Lana School of Public Health (T.K.Y.) and The Keenan Research Centre for Biomedical Science of St. Michael's Hospital (P.W.C.), and Department of Medicine, University of Toronto, Toronto, ON, Canada; Département de médecine sociale et preventive, Axe Santé des Populations et Pratiques Optimales en Santé, Centre de Recherche du CHU de Québec, Université Laval, QC, Canada (E.D.); and National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark (P.B.).
Background:
Inuit are considered to be vulnerable to cardiovascular disease because their lifestyles are becoming more Westernized. During sequence analysis of Inuit individuals at extremes of lipid traits, we identified 2 nonsynonymous variants in low-density lipoprotein receptor (LDLR), namely p.G116S and p.R730W.
Methods And Results:
Genotyping these variants in 3324 Inuit from Alaska, Canada, and Greenland showed they were common, with allele frequencies 10% to 15%. Only p.G116S was associated with dyslipidemia: the increase in LDL cholesterol was 0.54 mmol/L (20.9 mg/dL) per allele (P=5.6×10(-49)), which was >3× larger than the largest effect sizes seen with other common variants in other populations. Carriers of p.G116S had a 3.02-fold increased risk of hypercholesterolemia (95% confidence interval, 2.34-3.90; P=1.7×10(-17)), but did not have classical familial hypercholesterolemia. In vitro, p.G116S showed 60% reduced ligand-binding activity compared with wild-type receptor. In contrast, p.R730W was associated with neither LDL cholesterol level nor altered in vitro activity.
Conclusions:
LDLR p.G116S is thus unique: a common dysfunctional variant in Inuit whose large effect on LDL cholesterol may have public health implications.
Related Concept Videos
01:16Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
01:29Pharmacogenomics: Identification of New Drug Targets
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
01:27Principles of Pharmacogenetics: Types of Genetic Variants
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents