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Curr Atheroscler Rep. 2017 Jul;19(7):31. doi: 10.1007/s11883-017-0667-9.

Genetics of Triglycerides and the Risk of Atherosclerosis.

Dron JS1,2, Hegele RA3,4,5.

Author information

1
Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
2
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 4288A-1151 Richmond Street North, London, ON, N6A 5B7, Canada.
3
Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. hegele@robarts.ca.
4
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 4288A-1151 Richmond Street North, London, ON, N6A 5B7, Canada. hegele@robarts.ca.
5
Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. hegele@robarts.ca.

Abstract

PURPOSE OF REVIEW:

Plasma triglycerides are routinely measured with a lipid profile, and elevated plasma triglycerides are commonly encountered in the clinic. The confounded nature of this trait, which is correlated with numerous other metabolic perturbations, including depressed high-density lipoprotein cholesterol (HDL-C), has thwarted efforts to directly implicate triglycerides as causal in atherogenesis. Human genetic approaches involving large-scale populations and high-throughput genomic assessment under a Mendelian randomization framework have undertaken to sort out questions of causality.

RECENT FINDINGS:

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.

KEYWORDS:

Complex trait; DNA sequencing; Genetic association; Mendelian randomization; Monogenic; Polygenic

PMID:
28534127
PMCID:
PMC5440481
DOI:
10.1007/s11883-017-0667-9
[Indexed for MEDLINE]
Free PMC Article

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