@article{oai:kanazawa-u.repo.nii.ac.jp:00017887,
 author = {Inazu, Akihiro and 稲津, 明広},
 issue = {6},
 journal = {金沢大学十全医学会雑誌},
 month = {Dec},
 note = {The plasma high density lipoprotein (HDL) cholesterol is a protective factor in the development of atherosclerosis. Recently, a family with increased HDL cholesterol level was described to be defi­cient in cholesteryl ester transfer activity in plasma. Plasma cholesteryl ester transfer protein (CETP), a hydrophobic glycoprotein with Mr. 74,000, catalyzes the transfer of cholesteryl esters from HDL to other lipoproteins. Using monoclonal antibodies against human CETP, CETP was not detected in two siblings with increased HDL cholesterol level. They are homozygous for a point mutation in the 5'­splice donor site of the intron 14 of the gene for CETP, which is incompatible with normal splicing of pre-messenger RNA. Furthermore, the same splicing defect was identified in 9 unrelated families (at least one allele) out of 21 families with an increased HDL cholesterol level (>100 mg/dl) who had originated from four different regions of Japan (Hokuriku, Iwate, Hiroshima, and Tokyo). Analysis of the restriction fragment length polymorphism of the CETP gene showed that all probands of 5 CETP deficient families, were homozygous for the identical haplotype, which suggests that they may share a common genetic backgroud. Five family members with CETP deficiency were separated into three groups on the basis of the presence of the splicing defect (G→A mutation). Family members homozygous for CETP deficiency (n=10) had hypercholesterolemia (271土32 mg/dl, mean士S.D.), markedly increased levels of HDL cholesterol (164士39) and apolipoprotein A-I (213土47), and decreased levels of the low density lipoprotein cholesterol (77土31) and the apolipoprotein B (54士 14). All homozygotes showed enlarged HDL corresponding to HDL1 size (particle size: >12nm). They had polydispersed and finely distinct LDL subclasses (between IDL2 and LDlA), in which large LDL such as IDL2 and LDL1 and small LDL such as LDL4 were increased, and conversely LDL2 and LDL3 were decreased. Members heterozygous for the deficiency (n=20), whose CETP levels (1.4士0.3 mg/l）were in the lower part of the normal range (2.3 土 0.6), had slightly increased levels of HDL cholesterol (66土15) and apolipoprotein A-1 (149土43), and an increased ratio of HDL2 to HDL3 (1.5 土 0.8 vs. 0.6 土 0.4). There was no evidence of premature atherosclerosis in the families with CETP deficiency. Thus, the CETP deficiency appears to be a major cause of familial hyperalphalipopro­teinemia in Japan. The lipoprotein profile of subjects with CE1P deficiency is potentially anti­-atherogenic and may be associated with an increased life span.},
 pages = {1085--1101},
 title = {家族性高HDL血症における血漿コレステリルエステル転送蛋白に関する研究},
 volume = {100},
 year = {1991}
}