TY - JOUR

T1 - The polygenic nature of hypertriglyceridaemia

T2 - implications for definition, diagnosis, and management

AU - Hegele, Robert A

AU - Ginsberg, Henry N

AU - Chapman, M John

AU - Nordestgaard, Børge G

AU - Kuivenhoven, Jan Albert

AU - Averna, Maurizio

AU - Borén, Jan

AU - Bruckert, Eric

AU - Catapano, Alberico L

AU - Descamps, Olivier S

AU - Hovingh, G Kees

AU - Humphries, Steve E

AU - Kovanen, Petri T

AU - Masana, Luis

AU - Pajukanta, Päivi

AU - Parhofer, Klaus G

AU - Raal, Frederick J

AU - Ray, Kausik K

AU - Santos, Raul D

AU - Stalenhoef, Anton F H

AU - Stroes, Erik

AU - Taskinen, Marja-Riitta

AU - Tybjærg-Hansen, Anne

AU - Watts, Gerald F

AU - Wiklund, Olov

AU - European Atherosclerosis Society Consensus Panel

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

U2 - 10.1016/S2213-8587(13)70191-8

DO - 10.1016/S2213-8587(13)70191-8

M3 - Review

C2 - 24731657

VL - 2

SP - 655

EP - 666

JO - The Lancet Diabetes & Endocrinology

JF - The Lancet Diabetes & Endocrinology

SN - 2213-8587

IS - 8

ER -