May 23, 2017Current Atherosclerosis Reports107 citationsOpen Access
Genetics of Triglycerides and the Risk of Atherosclerosis
Structured PICO
Are common and rare variants in genes determining plasma triglycerides associated with clinical cardiovascular endpoints?
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Population
Populations from large-scale meta-analyses of cohorts and population-based sequencing studies
I
Intervention
Common and rare variants in genes determining plasma triglycerides (lipoprotein lipase, apo A-V, apo C-III, angiopoietin-like proteins 3 and 4)
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Outcome
Clinical cardiovascular endpointshard clinical
Genetic evidence supports a potential causal role for triglycerides in atherosclerosis, though confounding by low HDL-C or other metabolic disturbances cannot be fully excluded.
Abstract
We review recent large-scale meta-analyses of cohorts and population-based sequencing studies designed to address whether common and rare variants in genes whose products are determinants of plasma triglycerides are also associated with clinical cardiovascular endpoints. The studied loci include genes encoding lipoprotein lipase and proteins that interact with it, such as apolipoprotein (apo) A-V, apo C-III and angiopoietin-like proteins 3 and 4, and common polymorphisms identified in genome-wide association studies. Triglyceride-raising variant alleles of these genes showed generally strong associations with clinical cardiovascular endpoints. However, in most cases, a second lipid disturbance-usually depressed HDL-C-was concurrently associated. While the findings collectively shift our understanding towards a potential causal role for triglycerides, we still cannot rule out the possibilities that triglycerides are a component of a joint phenotype with low HDL-C or that they are but markers of deeper causal metabolic disturbances that are not routinely measured in epidemiological-scale genetic studies.