ANGPTL3 Deficiency Linked to Reduced CAD Risk

Heterozygous carriers of ANGPTL3 loss-of-function mutations have reductions in TGs, LDL-C
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MONDAY, April 3, 2017 (HealthDay News) -- Angiopoietin-like 3 (ANGPTL3) deficiency is associated with reduced risk of coronary artery disease (CAD), according to a study published online March 29 in the Journal of the American College of Cardiology.

Nathan O. Stitziel, M.D., Ph.D., from the Washington University School of Medicine in St. Louis, and colleagues used computed tomography angiography to examine coronary atherosclerotic burden in three individuals with complete ANGPTL3 deficiency and three wild-type first-degree relatives. In addition, ANGPTL3 loss-of-function (LOF) mutations, defined as nonsense, frameshift, and splice-site variants, along with missense variants, were ascertained in up to 21,980 individuals with CAD and 158,200 controls. In a biomarker study, circulating ANGPTL3 concentration was measured in 1,493 individuals presenting with myocardial infarction (MI) and 3,232 controls.

The researchers observed no evidence of coronary atherosclerotic plaque in the three individuals with complete ANGPTL3 deficiency. Approximately one in 309 individuals were heterozygous carriers for an LOF mutation in ANGPTL3 gene sequencing. Heterozygous carriers of ANGPTL3 LOF mutations demonstrated a 17 percent reduction in circulating triglycerides and a 12 percent reduction in low-density lipoprotein cholesterol, compared to those without mutations. Carrier status correlated with a reduction in the odds of CAD (odds ratio, 0.66). Individuals in the lowest versus the highest tertile of circulating ANGPTL3 concentrations had reduced odds of MI (adjusted odds ratio, 0.65).

"ANGPTL3 deficiency is associated with protection from CAD," the authors write.

Several authors disclosed financial ties to the pharmaceutical industry.

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