Apolipoprotein A-I deficiency with accumulated risk for CHD but no symptoms of CHD.
We evaluated a 69-year-old Japanese woman with apolipoprotein (apo) A-I deficiency, high levels of low-density lipoprotein (LDL)-cholesterol, hypertension and impaired glucose tolerance. The patient had corneal opacity, but neither xanthomas, xanthelasma, nor tonsillar hypertrophy. She was not symptomatic for coronary heart disease (CHD), and had normal electrocardiograms at rest and exercise using a cycle ergometer. She had severely reduced levels of high-density lipoprotein (HDL)-cholesterol (0.10-0.18 mmol/l) and no apo A-I (<0.6 mg/dl). LDL-cholesterol and apo B as well as apo E were increased even under treatment with 10 mg pravastatin per day. Gel filtration chromatography revealed that in addition to VLDL and LDL fractions, she had apo A-II rich and apo E rich fractions, which were present in the HDL fraction separated by ultracentrifugation. A cytosine deletion was identified by genomic DNA sequencing of the apo A-I gene of the patient at the third base of codon 184 in the fourth exon, which led to a frame shift mutation and early termination at codon 200. This patient is the oldest among those with apo A-I deficiency reported in the literature, and she had no symptoms of CHD despite the accumulated risk for the disease.
Yokota
Hiromitsu
H
Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan.
Hashimoto
Yoshiaki
Y
Okubo
Shigeo
S
Yumoto
Masato
M
Mashige
Fumiko
F
Kawamura
Mitsunobu
M
Kotani
Kazuo
K
Usuki
Yasuteru
Y
Shimada
Sachiyo
S
Kitamura
Kiyoshi
K
Nakahara
Kazuhiko
K
D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D016632:Apolipoprotein A-I / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D001057:Apolipoproteins E / Q000097:blood; D001483:Base Sequence / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D003596:Cytosine; D005260:Female; D017353:Gene Deletion; D018149:Glucose Intolerance / Q000150:complications; D006801:Humans; D006973:Hypertension / Q000150:complications; D008074:Lipoproteins / Q000097:blood; D008661:Metabolism, Inborn Errors / Q000150:complications; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012307:Risk Factors
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D003596:Cytosine