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.
Katsuda
Shoji
S
Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, 13-1Takara-machi, Kanazawa, 920-8641 Japan.
Kawashiri
Masa-Aki
MA
Inazu
Akihiro
A
Tada
Hayato
H
Tsuchida
Masayuki
M
Kaneko
Yoshibumi
Y
Nozue
Tsuyoshi
T
Nohara
Atsushi
A
Okada
Toshihide
T
Kobayashi
Junji
J
Michishita
Ichiro
I
Mabuchi
Hiroshi
H
Yamagishi
Masakazu
M
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