title: Cholesteryl ester transfer protein gene: two common mutations and their effect on plasma high-density lipoprotein cholesterol content.
abstract: Cholesteryl ester transfer protein regulates high-density lipoprotein cholesterol (HDL-C) level, and genetic deficiency causes hyperalphalipoproteinemia (HALP). The G to A mutation in the intron 14 splice donor (I14A) has been known to be a common mutation in HALP. Recently, another mutant, D442G (Asp 442 to Gly), was ascertained. The allelic frequencies of I14A and D442G were investigated using 226 unrelated patients with HDL-C of 1.03 mmol/L (40 mg/dL) or greater. Of these, 44 had a mutation I14A and/or D442G. The I14A was found in 15, including 4 compound heterozygotes (I14A/D442G) in patients with HDL-C of 2.05 mmol/L (80 mg/dL) or greater. All I14A homozygotes (n = 5) were present in the group with HDL-C of 3.08 mmol/L (120 mg/dL) or greater, and the allelic frequency paralleled the increase in HDL-C level. D442G was identified in 33, including the 4 compound heterozygotes. Its allelic frequency appeared as two clusters, one at HDL-C around 1.79-2.03 mmol/L (70-79 mg/dL) and the other at HDL-C of 2.82 mmol/L (110 mg/dL) or greater; the latter consisted exclusively of compound heterozygotes. Allelic frequency in the general population for I14A and D442G was 0.81% and 4.62%, respectively. These data suggest that D442G is a common mutation and that, although I14A is responsible for the most severe HALP, D442G leads to a relatively smaller increase in HDL-C.
authors.affiliation: Department of Laboratory Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Akita
authors.forename: H
authors.initials: H
authors.lastname: Chiba
authors.forename: K
authors.initials: K
authors.lastname: Tsuchihashi
authors.forename: M
authors.initials: M
authors.lastname: Tsuji
authors.forename: M
authors.initials: M
authors.lastname: Kumagai
authors.forename: K
authors.initials: K
authors.lastname: Matsuno
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D004252:DNA Mutational Analysis; D004262:DNA Restriction Enzymes; D004587:Electrophoresis, Agar Gel; D005260:Female; D005787:Gene Frequency; D006023:Glycoproteins; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D006023:Glycoproteins; D004262:DNA Restriction Enzymes