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 -