title: A novel missense mutation (L296 Q) in cholesteryl ester transfer protein gene related to coronary heart disease.
abstract: Cholesteryl ester transfer protein (CETP) is a key participant in the reverse transport of cholesterol from the peripheral tissues to the liver. To understand further the role that CETP gene plays in the pathogenesis of coronary heart disease (CHD), the promoter region, all 16 exons and adjacent intronic regions of CETP gene were screened for single nucleotide polymorphisms (SNPs) in 203 CHD patients and 209 healthy volunteers by the combination of PCR, denaturing high performance liquid chromatography (DHPLC), molecular cloning, and DNA sequencing. A novel missense mutation in the CETP gene was identified. This mutation (L(296)Q) was caused by a T-to-A conversion at codon 296 of exon 10 which resulted in the replacing of the codon for leucine (CTG) with the codon for glutamine (CAG). Further studies found that there was a significant increase in the mutant allele frequency in the CHD patients compared with that in the controls (0.160 vs. 0.091,cgr;(2) = 9.014, P = 0.003), and the odds ratio to develop CHD was 1.83 for the (296)Q allele carriers vs. (296)LL homozygotes. Statistical analyses also demonstrated that the mutant (296)Q allele carrier patients displayed significantly higher total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) concentrations than noncarrier patients. All these results suggest that the Q(296) mutation in CETP gene was closely related to CHD, and the identification of new mutations in the CETP gene will afford the opportunity to investigate the relationship between CETP gene and CHD.
authors.affiliation: Department of Medical Genetics, West China Hospital; Division of Human Morbid Genomics, Key Laboratory of Biotherapy of Human Diseases of Ministry of Education, Sichuan University, Chengdu 610041, China. szzhang@mcwcum.com
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Zheng
authors.forename: Si-Zong
authors.initials: SZ
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: De-Jia
authors.initials: DJ
authors.lastname: Huang
authors.forename: Lin-Chuan
authors.initials: LC
authors.lastname: Liao
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hou
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D002681:China; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006023:Glycoproteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense / Q000235:genetics; D010641:Phenotype; D020539:Sequence Analysis, Protein
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL; D006023:Glycoproteins; D002784:Cholesterol