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

Robert A. Hegele, Henry N. Ginsberg, M. John Chapman, Børge G. Nordestgaard, Jan Albert Kuivenhoven, Maurizio Averna, Jan Borén, Eric Bruckert, Alberico L. Catapano, Olivier S. Descamps, G. Kees Hovingh, Steve E. Humphries, Petri T. Kovanen, Luis Masana, Päivi Pajukanta, Klaus G. Parhofer, Frederick J. Raal, Kausik K. Ray, Raul D. Santos, Anton F H StalenhoefErik Stroes, Marja Riitta Taskinen, Anne Tybjærg-Hansen, Gerald F. Watts, Olov Wiklund

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)655-666
Number of pages12
JournalThe Lancet Diabetes and Endocrinology
Issue number8
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Endocrinology

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    Hegele, R. A., Ginsberg, H. N., Chapman, M. J., Nordestgaard, B. G., Kuivenhoven, J. A., Averna, M., Borén, J., Bruckert, E., Catapano, A. L., Descamps, O. S., Hovingh, G. K., Humphries, S. E., Kovanen, P. T., Masana, L., Pajukanta, P., Parhofer, K. G., Raal, F. J., Ray, K. K., Santos, R. D., ... Wiklund, O. (2014). The polygenic nature of hypertriglyceridaemia: Implications for definition, diagnosis, and management. The Lancet Diabetes and Endocrinology, 2(8), 655-666.