title: Molecular mechanisms of cholesteryl ester transfer protein deficiency in Japanese.
abstract: Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins. Since CETP regulates the plasma levels of HDL cholesterol and the size of HDL particles, CETP is considered to be a key protein in reverse cholesterol transport (RCT), a protective system against atherosclerosis. The importance of plasma CETP in lipoprotein metabolism was demonstrated by the discovery of CETP-deficient subjects with marked hyperalphalipoproteinemia (HALP). Genetic CETP deficiency is the most important and common cause of HALP in the Japanese. Ten mutations of the CETP gene have been demonstrated as causes of HALP, including two common mutations: an intron 14 splicing defect (Int14 + 1 G --> A) and an exon 15 missense mutation (D442G). The subjects with CETP deficiency show a variety of abnormalities in the concentration, composition, and function of both HDL and low density lipoprotein (LDL). CETP deficiency is considered a physiological state of impaired RCT, which may possibly lead to the development of atherosclerosis despite high HDL cholesterol levels. However, the pathophysiological significance of CETP in terms of atherosclerosis has been controversial. Epidemiological studies in Japanese-Americans living in Hawaii and Japanese in the Omagari area, where HALP subjects with an intron 14 splicing defect of the CETP gene are markedly frequent, have shown a relatively increased incidence of coronary atherosclerosis in CETP deficiency. On the other hand, the TaqIB polymorphism-B2 allele with low CETP mass and increased HDL cholesterol has been related to a decreased risk for coronary heart disease (CHD) in many studies, including the Framingham Offspring Study. The current review focused on the characterization of the Japanese subjects with CETP deficiency, including our recent findings.
authors.affiliation: Department of Advanced Technology and Development, BML, Inc., Saitama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagano
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirano
authors.forename: Mayumi
authors.initials: M
authors.lastname: Takano
authors.forename: Takao
authors.initials: T
authors.lastname: Maruyama
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ishihara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sagehashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kujiraoka
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hattori
authors.forename: Naohiko
authors.initials: N
authors.lastname: Sakai
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nakajima
authors.forename: Tohru
authors.initials: T
authors.lastname: Egashira
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000293:Adolescent; D000328:Adult; D001161:Arteriosclerosis / Q000150:complications; D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D005260:Female; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D006951:Hyperlipoproteinemias / Q000209:etiology / Q000235:genetics*; D007564:Japan; D050356:Lipid Metabolism; D008297:Male; D008659:Metabolic Diseases / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D012720:Severity of Illness Index
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins