MON-097 Angiopoietin-Like Protein 8 (ANGPTL8) Levels in Thai Subjects with Hyperalphalipoproteinemia

Abstract

Background Hyperalphalipoprtoteinemia (HALP) is primarily caused by loss-of-function mutations in key genes in the reverse cholesterol transport pathway (RCT) such as cholesteryl ester transfer protein, hepatic lipase, and endothelial lipase. Angiopoietin-like protein 3 (ANGPTL3) is a natural inhibitor of hepatic lipase and endothelial lipase. We have previously shown that ANGPTL3 levels are higher in HALP subjects compared to those of control. Angiopoietin-like protein 8 (ANGPTL8) is known to promote ANGPTL3 function. We aimed to examine ANGPTL8 levels in Thai HALP subjects. Methods Ninety subjects with HDL-cholesterol at least 100 mg/dl without other secondary causes, defined as HALP group, and ninety age-matched healthy controls were recruited from our outpatient clinic of tertiary university hospital. Clinical characteristics and lipid profiles of each group were obtained. Plasma ANGPTL8 levels were measured by ELISA. Results The mean age of the HALP subjects (91% female) was 58 ± 11 years. The mean HDL-cholesterol level in HALP group was significantly higher than that of the healthy controls (99 ± 17 mg/dl vs. 51 ± 6 mg/dl, p<0.001). The mean triglyceride level and LDL-cholesterol level in the HALP group were significantly lower than those of the controls (73 ± 31 mg/dl vs. 123 ± 50 mg/dl, p<0.001 and 131 ± 35 mg/dl vs. 144 ± 34 mg/dl, p=0.018, respectively). The mean plasma ANGPTL8 level was significantly higher in the HALP group compared to that of the controls (30.30 ± 10.80 ng/ml vs. 19.68 ± 7.81 ng/ml, p<0.001). HDL-cholesterol level was significantly correlated with plasma ANGPTL8 level in both groups (r=0.461, p<0.001). Plasma ANGPTL3 was the better determinant of HDL-cholesterol level than ANGPTL8. There was no significant correlation between plasma ANGPTL3 and ANGPTL8 levels (r=0.068, p=0.361). Conclusion Plasma ANGPTL8 levels in the HALP group were significantly higher than those of the healthy control and were significantly correlated with HDL-cholesterol levels. ANGPTL8 may be a potential determinant of HDL-cholesterol levels in Thai HALP subjects.