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Lancet Diabetes Endocrinol. 2014 Aug;2(8):655-66. doi: 10.1016/S2213-8587(13)70191-8. Epub 2013 Dec 23.

The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management.

Author information

  • 1Department of Medicine, Western University, London, ON, Canada. Electronic address: hegele@robarts.ca.
  • 2Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA.
  • 3Dyslipidaemia and Atherosclerosis Research Unit, INSERM U939, Pitié-Salpêtrière University Hospital, Paris, France.
  • 4Department of Diagnostic Sciences, Herlev Hospital, University of Copenhagen, Denmark.
  • 5Department of Molecular Genetics, University Medical Center Groningen, University of Groningen, Netherlands.
  • 6Department of Internal Medicine, University of Palermo, Palermo, Italy.
  • 7Strategic Research Center, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden.
  • 8Department of Endocrinology and Metabolism, Endocrinology and Cardiovascular Disease Prevention, Hôpital Pitié-Salpêtrière, Paris, France.
  • 9Department of Pharmacological Sciences, University of Milan and Multimedica IRCSS, Milan, Italy.
  • 10Centre de Recherche Médicale, Lipid Clinic, Hopital de Jolimont, Haine Saint-Paul, Belgium.
  • 11Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
  • 12Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
  • 13Wihuri Research Institute, Helsinki, Finland.
  • 14Vascular Medicine and Metabolism Unit, Sant Joan University Hospital, Universitat Rovira & Virgili, IISPV, CIBERDEM, Reus, Spain.
  • 15Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • 16Department of Endocrinology and Metabolism, University of Munich, Munich, Germany.
  • 17Division of Endocrinology and Metabolism, Director of the Carbohydrate and Lipid Metabolism Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
  • 18Cardiovascular Sciences Research Centre, St George's Hospital NHS Trust, London, UK.
  • 19Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
  • 20Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
  • 21Cardiovascular Research Group, Heart and Lung Centre, Helsinki University Central Hospital and Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
  • 22Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • 23School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA, Australia.
  • 24Department of Cardiology, Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract

Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk.

Copyright © 2014 Elsevier Ltd. All rights reserved.

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PMID:
24731657
[PubMed - in process]
PMCID:
PMC4201123
[Available on 2015-08-01]
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