Post-prandial remnant lipoprotein metabolism in autosomal recessive hypercholesterolaemia

• Published in: European journal of clinical investigation Vol. 42; no. 10; pp. 1094 - 1099
• Main Authors: Tada, Hayato, Kawashiri, Masa-aki, Tanaka, Akira, Nakano, Takamitsu, Nakajima, Katsuyuki, Inoue, Takeshi, Noguchi, Tohru, Nakanishi, Chiaki, Konno, Tetsuo, Hayashi, Kenshi, Nohara, Atsushi, Inazu, Akihiro, Kobayashi, Junji, Mabuchi, Hiroshi, Yamagishi, Masakazu
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2012; Wiley-Blackwell
• Subjects: Area Under Curve; Autosomal recessive hypercholesterolaemia; Biological and medical sciences; Cholesterol - metabolism; Disorders of blood lipids. Hyperlipoproteinemia; Enzyme-Linked Immunosorbent Assay; familial hypercholesterolaemia; Female; General aspects; Heterozygote; Humans; Hyperlipoproteinemia Type II - metabolism; LDLR adaptor protein 1; Lipoproteins - metabolism; Male; Medical sciences; Metabolic diseases; Middle Aged; oral fat tolerance test; Postprandial Period - physiology; remnant-like-particles; Triglycerides - metabolism; Autosomal recessive hypercholesterolaemia; Oral administration; remnant-like-particles; Tolerance; Metabolic diseases; Exploration; Lipids; Hyperlipoproteinemia; Autosome; oral fat tolerance test; Lipoprotein; Adaptor protein; Metabolism; LDLR adaptor protein 1; Cholesterol; Genetic disease; Medicine; Particle; Persistence; Hypercholesterolemia; familial hypercholesterolaemia; Fat; Inheritance(genetics); Dyslipemia
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2012.02700.x

Eur J Clin Invest 2012; 42 (10): 1094–1099 Background  Phenotype of autosomal recessive hypercholesterolaemia (ARH), a rare lipid disorder, is known to be milder than that of homozygous familial hypercholesterolaemia (FH) with LDL receptor gene mutation. However, few data exist regarding the functional differences in ARH and FH particularly in terms of remnant‐like particles’ (RLP) metabolism. Materials and methods  Blood sampling was performed up to 6 h after OFTT cream loading (50 g/body surface area) with 2‐h intervals in a single ARH proband, four heterozygous FH patients with LDL receptor gene mutation and four normal controls. Plasma lipoprotein and RLP fraction were determined by HPLC system. The area under curve (AUC) of each lipoprotein including RLP fractions was evaluated. Results  The AUC of TG, RLP cholesterol (RLP‐C) and RLP triglyceride (RLP‐TG) levels of heterozygous FH subjects was significantly higher than those of controls (466 ± 71 mg/dL × h vs. 303 ± 111 mg/dL × h, P < 0·05; 35 ± 7 mg/dL × h vs. 21 ± 8 mg/dL × h, P < 0·05; 124 ± 57 mg/dL × h vs. 51 ± 13 mg/dL×h, P < 0·05, respectively). Under these conditions, those values of ARH were close to those of controls (310 mg/dL × h, 22 mg/dL × h, 23 mg/dL × h, respectively). Conclusion  These data demonstrate that unlike in FH, RLP clearance is preserved in ARH. The preservation of post‐prandial RLP clearance may contribute to the mild phenotype of ARH compared with FH.