Apolipoprotein B gene mutations and fatty liver in Japanese hypobetalipoproteinemia.
BACKGROUND
Familial hypobetalipoproteinemia (FHBL) is a hereditary disorder characterized by decreased plasma concentrations of low-density lipoprotein cholesterol. The best-characterized causes of FHBL are apolipoprotein B (apoB) gene mutations, which produce truncated apoB proteins. Fatty liver is thought to be frequent in FHBL, owing to impaired secretion of very-low-density lipoprotein from the liver. Homozygotes for FHBL present with extremely low concentrations of plasma lipids, and may suffer from deficiencies of fat-soluble vitamins. The objectives of this study were to identify apoB-defective FHBL subjects and investigate fatty liver in Japanese population.


METHODS
We screened 14 hypocholesterolemic subjects for apoB gene mutations by PCR-SSCP and performed liver ultrasonography in a Japanese population.


RESULTS
We identified an apoB-82 homozygote in one subject and an apoB-13.7 heterozygote in another subject. Four of 6 individuals with FHBL presented with fatty liver in those 2 FHBL families. Liver biopsy of the apoB-13.7 heterozygote, which had obesity and insulin resistance, showed severe fatty liver. The apoB-82 homozygote was asymptomatic with fat-soluble vitamin concentrations being normal, possibly due to spared secretion of apoB-48 from the intestine and increased plasma concentrations of high-density lipoprotein cholesterol.


CONCLUSIONS
ApoB gene mutations might not be rare and that fatty liver might be frequent in Japanese FHBL.
Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, 13-1Takara-machi, Kanazawa, 920-8641 Japan.
Shoji
S
Katsuda
Masa-Aki
MA
Kawashiri
Akihiro
A
Inazu
Hayato
H
Tada
Masayuki
M
Tsuchida
Yoshibumi
Y
Kaneko
Tsuyoshi
T
Nozue
Atsushi
A
Nohara
Toshihide
T
Okada
Junji
J
Kobayashi
Ichiro
I
Michishita
Hiroshi
H
Mabuchi
Masakazu
M
Yamagishi
D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D008078:Cholesterol, LDL / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009765:Obesity / Q000235:genetics; D014463:Ultrasonography
D001055:Apolipoproteins B; D008078:Cholesterol, LDL