Higher frequency of abnormal serum angiopoietin-like protein 3 than abnormal cholesteryl ester transfer protein in Japanese hyperalphalipoproteinemic subjects.

BACKGROUND: Either a decrease of cholesteryl ester transfer protein (CETP) or an increase of angiopoietin-like protein 3 (ANGPTL3) in plasma has been shown to increase HDL-cholesterol (HDL-C) levels. However, as yet, it is not known which protein is more strongly associated with the modulation of HDL in the Japanese hyperalphalipoproteinemic (HALT) subjects. METHODS: The serum concentration of ANGPTL3 and CETP, together with total cholesterol (TC), triglycerides (TG), adiponectin and ApoE phenotypes were determined in three groups with different HDL-C concentrations: low, <40 mg/dl (n=51); normal, 40-90 mg/dl (n=126) and high, >90 mg/dl (n=89) in the average Japanese population. RESULTS: The normal range (mean+/-2SD) of serum ANGPTL3 (218+/-144 ng/ml) and CETP (1.29+/-0.90 microg/ml) were determined in cases with 40-90 mg/dl HDL-C concentration. The frequency of abnormally high ANGPTL3 cases (>362 ng/ml) were found to be significantly greater (44%) compared with those of low CETP cases (<0.39 microg/ml, 4.5%) in HALT cases (>90 mg/dl). ANGPTL3 showed a high correlation with HDL-C (r=0.67, P<0.0001) and adiponectin (r=0.57, P<0.0001), but not with CETP. CONCLUSION: In average Japanese population, abnormally higher frequency of increased ANGPTL3 prevail in HALT cases as compared with cases with low CETP. These findings suggest that ANGPTL3, the inhibitor of endothelial lipase, may be more strongly associated with increased HDL-C rather than CETP in plasma. Accordingly, ANGPTL3 seems to be a better target for the modulation of HDL-C.

Serum remnant lipoprotein cholesterol/triglyceride ratio as an index for screening familial type III hyperlipidaemia.

BACKGROUND: An elevated serum remnant lipoprotein cholesterol (RLP-C)/triglyceride (TG) ratio has not been evaluated as an index of familial type III hyperlipidaemia defined by the presence of beta-VLDL and apolipoprotein (Apo) E2/2 phenotype in the Japanese hyperlipidaemic population. METHODS: Serum lipids and lipoproteins from 514 individuals (200 men and 314 women, mean age 58 years) with total cholesterol >6.22 mmol/L and TG between 2.26 mmol/L and 9.04 mmol/L, selected from 25,080 subjects visiting the clinics for health checkup were analysed for a possible relationship with familial type III hyperlipoproteinaemia. RESULTS: Median RLP-C concentration and RLP-C/TG ratio were 0.30 and 0.11 mmol/L, respectively. When compared between subjects with (31 cases) and without (483 cases) a broad-beta band on electrophoresis, the RLP-C concentrations and RLP-C/TG ratio were 0.77 +/- 0.43 mmol/L versus 0.34 +/- 0.16 mmol/L (P<0.0001) and 0.15 +/- 0.023 versus 0.11 +/- 0.027 (P<0.0001), respectively. Three cases with broad-beta band positive (the presence of beta-VLDL) showed RLP-C/TG ratio greater than 0.23 and RLP-C greater than 0.78 mmol/L, suggestive of type III hyperlipoproteinaemia, despite a lack of characteristic Apo E2/2 homozygosity. Cases with Apo E/Apo CIII ratio greater than 1.0 were not detected in this study group. CONCLUSION: Serum RLP-C concentration and RLP-C/TG ratio, together with Apo E/Apo CIII ratio appear to be useful for screening familial type III hyperlipidaemia in the Japanese hyperlipidaemic population.