Genetic determinants of plasma triglycerides
Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might h...
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doaj-e66a5812eef4422390c580ddfe66dd352021-04-28T06:02:44ZengElsevierJournal of Lipid Research0022-22752011-02-01522189206Genetic determinants of plasma triglyceridesChristopher T. Johansen0Sekar Kathiresan1Robert A. Hegele2Departments of Biochemistry and Medicine, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 5K8, CanadaCenter for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114; Department of Medicine, Harvard Medical School, Boston, MA 02114; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142To whom correspondence should be addressed hegele@robarts.ca; Departments of Biochemistry and Medicine, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 5K8, CanadaPlasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ∼10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies.http://www.sciencedirect.com/science/article/pii/S0022227520405152hypertriglyceridemiahypotriglyceridemiadyslipidemiasgenetic variationgenomicslipoproteins |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christopher T. Johansen Sekar Kathiresan Robert A. Hegele |
spellingShingle |
Christopher T. Johansen Sekar Kathiresan Robert A. Hegele Genetic determinants of plasma triglycerides Journal of Lipid Research hypertriglyceridemia hypotriglyceridemia dyslipidemias genetic variation genomics lipoproteins |
author_facet |
Christopher T. Johansen Sekar Kathiresan Robert A. Hegele |
author_sort |
Christopher T. Johansen |
title |
Genetic determinants of plasma triglycerides |
title_short |
Genetic determinants of plasma triglycerides |
title_full |
Genetic determinants of plasma triglycerides |
title_fullStr |
Genetic determinants of plasma triglycerides |
title_full_unstemmed |
Genetic determinants of plasma triglycerides |
title_sort |
genetic determinants of plasma triglycerides |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2011-02-01 |
description |
Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ∼10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies. |
topic |
hypertriglyceridemia hypotriglyceridemia dyslipidemias genetic variation genomics lipoproteins |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520405152 |
work_keys_str_mv |
AT christophertjohansen geneticdeterminantsofplasmatriglycerides AT sekarkathiresan geneticdeterminantsofplasmatriglycerides AT robertahegele geneticdeterminantsofplasmatriglycerides |
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