title: The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management.
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.
authors.affiliation: Department of Medicine, Western University, London, ON, Canada. Electronic address: hegele@robarts.ca.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.affiliation: Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA.
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
authors.affiliation: Dyslipidaemia and Atherosclerosis Research Unit, INSERM U939, Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: Department of Diagnostic Sciences, Herlev Hospital, University of Copenhagen, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Department of Molecular Genetics, University Medical Center Groningen, University of Groningen, Netherlands.
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.affiliation: Department of Internal Medicine, University of Palermo, Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.affiliation: Strategic Research Center, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.affiliation: Department of Endocrinology and Metabolism, Endocrinology and Cardiovascular Disease Prevention, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.affiliation: Department of Pharmacological Sciences, University of Milan and Multimedica IRCSS, Milan, Italy.
authors.forename: Alberico L
authors.initials: AL
authors.lastname: Catapano
authors.affiliation: Centre de Recherche Médicale, Lipid Clinic, Hopital de Jolimont, Haine Saint-Paul, Belgium.
authors.forename: Olivier S
authors.initials: OS
authors.lastname: Descamps
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.affiliation: Vascular Medicine and Metabolism Unit, Sant Joan University Hospital, Universitat Rovira & Virgili, IISPV, CIBERDEM, Reus, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Masana
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Päivi
authors.initials: P
authors.lastname: Pajukanta
authors.affiliation: Department of Endocrinology and Metabolism, University of Munich, Munich, Germany.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Parhofer
authors.affiliation: Division of Endocrinology and Metabolism, Director of the Carbohydrate and Lipid Metabolism Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Raal
authors.affiliation: Cardiovascular Sciences Research Centre, St George's Hospital NHS Trust, London, UK.
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.affiliation: Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Stroes
authors.affiliation: Cardiovascular Research Group, Heart and Lung Centre, Helsinki University Central Hospital and Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.affiliation: School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: Department of Cardiology, Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Olov
authors.initials: O
authors.lastname: Wiklund
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003131:Combined Modality Therapy; D020022:Genetic Predisposition to Disease; D006293:Health Promotion; D006801:Humans; D015228:Hypertriglyceridemia / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D008019:Life Style; D020412:Multifactorial Inheritance; D017410:Practice Guidelines as Topic; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D014280:Triglycerides
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