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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

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

Comment in

PMID:
24731657
PMCID:
PMC4201123
DOI:
10.1016/S2213-8587(13)70191-8
[Indexed for MEDLINE]
Free PMC Article

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