Journal
JOURNAL OF LIPID RESEARCH
Volume 52, Issue 2, Pages 189-206Publisher
ELSEVIER
DOI: 10.1194/jlr.R009720
Keywords
hypertriglyceridemia; hypotriglyceridemia; dyslipidemias; genetic variation; genomics; lipoproteins; resequencing
Categories
Funding
- Canadian Institutes of Health Research (CIHR) [MOP-13430, MOP-79523, CTP-79853]
- Heart and Stroke Foundation of Ontario [NA-6059, T-6018, PRG-4854]
- Pfizer
- Genome Canada through the Ontario Genomics Institute
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Plasma triglyceride (TG) concentration is re-emerging 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 similar to 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.-Johansen, C. T., S. Kathiresan, and R. A. Hegele. Genetic determinants of plasma triglycerides. J. Lipid Res. 2011. 52: 189-206.
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