1. Atherosclerotic cardiovascular disease in hyperalphalipoproteinemia due to LIPG variants
- Author
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Bharati Dhanluxmi Ratanjee, Gabriele Solomon, Justine Cole, Ryan Benjamin, D.M. Blackhurst, and Adrian David Marais
- Subjects
Endothelial lipase ,Adult ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030204 cardiovascular system & hematology ,Gastroenterology ,Lipid Metabolism, Inborn Errors ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,High-density lipoprotein ,Internal medicine ,Internal Medicine ,Medicine ,Humans ,030212 general & internal medicine ,Nutrition and Dietetics ,business.industry ,Vascular disease ,Atherosclerotic cardiovascular disease ,Cholesterol ,Cholesterol, HDL ,Middle Aged ,medicine.disease ,Cholesterol Ester Transfer Proteins ,Residual risk ,chemistry ,Intima-media thickness ,Cardiovascular Diseases ,Cohort ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background High density lipoprotein cholesterol (HDL-C) concentration correlates inversely with atherosclerotic cardiovascular disease (ASCVD) risk and is included in risk calculations. Endothelial lipase (EL) is a phospholipase that remodels HDL. Deficiency of EL due to mutations in its gene, LIPG, is associated with hyperalphalipoproteinemia. The effects of EL on HDL function and ASCVD risk remain poorly understood. Objectives To determine whether hyperalphalipoproteinemia due to EL deficiency is protective against ASCVD. Methods We identified LIPG variants amongst patients with severe hyperalphalipoproteinemia (HDL-C >2.5 mmol/L) attending a referral lipid clinic in the Western Cape Province of South Africa. We analysed the clinical and biochemical phenotypes amongst primary hyperalphalipoproteinemia cases (males HDL-C >1.6 mmol/L; females HDL-C >1.8 mmol/L) due to LIPG variants, and the distribution of variants in normal and hyperalphalipoproteinemia ranges of HDL-C. Results 1007 patients with HDL-C concentration ranging from 1.2 to 4.5 mmol/L were included. Seventeen females had primary hyperalphalipoproteinemia. Vascular disease was prominent, but not associated with HDL-C concentration, LDL-C concentration or carotid artery intima media thickness. Two novel and three known LIPG variants were identified in severe hyperalphalipoproteinemia. Four additional variants were identified in the extended cohort. Two common variants appeared normally distributed across the HDL-C concentration range, while six less-common variants were found only at higher HDL-C concentrations. One rare variant had a moderate effect. Conclusion Hyperalphalipoproteinemia due to LIPG variants is commoner in females and may not protect against ASCVD. Use of current risk calculations may be inappropriate in patients with hyperalphalipoproteinemia due to EL deficiency. Our study cautions targeting EL to reduce risk.
- Published
- 2020