Carriers of loss-of-function variants in ANGPTL3 have a reduced risk of coronary artery disease and reduced plasma levels of triglycerides and LDL-C, while carriers of loss-of-function variants in ANGPTL4 have a reduced risk of coronary artery disease and reduced plasma levels of triglycerides and increased HDL-C.
One protein that raises plasma triglyceride levels and that has emerged as a modulator of coronary artery disease risk is angiopoietin-like 4 (ANGPTL4).
This study aimed to assess the association between the angiopoietin-like protein 4 gene (<i>ANGPTL4</i>) single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS), and response to atorvastatin therapy in a Southern Chinese Han population.
The 40Lys variant in ANGPTL4 was associated with protection from coronary disease and type 2 diabetes in groups with genetically higher or lower LDL-C. For a genetic difference of 0.23 SDs in LDL-C, ANGPTL3 loss-of-function variants, which also have beneficial associations with LPL lipolysis, were associated with greater protection against coronary disease than other LDL-C-lowering genetic mechanisms (ANGPTL3 loss-of-function variants: odds ratio, 0.66; 95% CI, 0.52-0.83; 58 LDL-C-lowering variants: odds ratio, 0.90; 95% CI, 0.89-0.91; P for heterogeneity = .009).
We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
Finally, we found that the expression of peroxisome proliferator-activated receptor δ (PPARδ), Adipose Differentiation-Related Protein (ADRP), and Angiopoietin-like 4 (ANGPTL4) were affected by LncPPARδ silencing.Our present study indicated that LncPPARδ, especially combined with risk factors, can be a good biomarker for CAD.
Carriers of E40K and other inactivating mutations in ANGPTL4 had lower levels of triglycerides and a lower risk of coronary artery disease than did noncarriers.
We examined the association of plasma ANGPTL4 levels with the metabolic syndrome (harmonized consensus definition), with angiographically determined coronary artery disease (CAD), and with the risk of future cardiovascular events in a cohort of 490 patients undergoing coronary angiography for the evaluation of stable CAD.