Post-prandial remnant lipoprotein metabolism in autosomal recessive hypercholesterolaemia.
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.


METHODS
Blood sampling was performed up to 6h 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).


CONCLUSIONS
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.
Division of Cardiovascular Medicine Kanazawa University Graduate School of Medicine, Kanazawa, Japan. ht240z@sa3.so-net.ne.jp
Hayato
H
Tada
Masa-Aki
MA
Kawashiri
Akira
A
Tanaka
Takamitsu
T
Nakano
Katsuyuki
K
Nakajima
Takeshi
T
Inoue
Tohru
T
Noguchi
Chiaki
C
Nakanishi
Tetsuo
T
Konno
Kenshi
K
Hayashi
Atsushi
A
Nohara
Akihiro
A
Inazu
Junji
J
Kobayashi
Hiroshi
H
Mabuchi
Masakazu
M
Yamagishi
D019540:Area Under Curve; D002784:Cholesterol / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism*
D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol