Cholesterol ester transfer protein (CETP) is a key regulator of high density lipoprotein (HDL). Owing to its important role in the reverse of cholesterol transport, CETP has become a hotspot target in modulating lipid drug design. In this paper, structure based pharmacophore (SBP) models for CETP inhibitors were built based on the protein structure 4F2A from Protein Database (PDB). The best pharmacophore contained six hydrophobic features, one hydrogen bond acceptor feature and nine excluded volume features, with the N and CAI value was 3.33 and 2.31 respectively. Then the model was used to search the traditional Chinese medicine database (TCMD) and 629 compounds originated from 315 TCM herbs were obtained. Molecular docking was also used to validate SBP by analyzing the critical amino acid residue and the interaction between potential active compounds and receptor. In this study, several TCM herbs, like Lycii Frutus and Schisandrae chinensis fructus, which contained more optimal SBP based screening results, have been reported hypolipidemic effect, and need to be studied deeply in a more focused research on herbal active constituents. Therefore, this study could provide reliable fundamental data for exploring the action mechanisms of TCM, and be applicable to identify lead candidates, which can be utilized as starting scaffolds for natural CETP inhibitors.
Cholesterol Ester Transfer Proteins ; antagonists & inhibitors ; Drug Evaluation, Preclinical ; methods ; Medicine, Chinese Traditional ; Molecular Docking Simulation

OBJECTIVESTo detect the cholesterol ester transfer protein (CETP) levels in semen of infertile patients and evaluate the correlation between CETP in semial plasma and infertility.

METHODSOne hundred and sixty-three infertile patients and fifteen fertile males were selected randomly. The routine examination of ejaculates was fulfilled by computer aided semen analysis (CASA). The CETP levels in all seminal plasma samples and fifty-five serum samples were detected by ELISA method.

RESULTSThe CETP levels in infertile patients and fertile males were (2.21 +/- 1.23) microgram/L and (1.40 +/- 0.45) microgram/L, respectively. There were no significant differences between the two groups(P > 0.05). And there were no significant differences of CETP levels in seminal plasma among groups of azoospermia(n = 29), oligoasthenozoospermia (n = 58), oligospermia(n = 15), asthenozoospermia(n = 44) and normozoospermia(n = 17) in the infertile patients(P > 0.05). The CETP in seminal plasma and serum were detected in 55 infertile patients, and there was no correlation between CETP levels in seminal plasma and serum using Spearman analysis(r = 0.009, P > 0.05). The mean CETP level in seminal plasma was almost 1/1,000 of that in serum.

CONCLUSIONSThe CETP level in seminal plasma is extremely low and has no relation with the changes of sperm density or motility. It may ensure the integrity of sperm membrane before the sperm enters into female genital tract.

Adult ; Carrier Proteins ; analysis ; blood ; Cholesterol Ester Transfer Proteins ; Glycoproteins ; Humans ; Infertility, Male ; metabolism ; Male ; Middle Aged ; Semen ; chemistry

BACKGROUND AND OBJECTIVES: Cholesteryl ester transfer protein (CETP) plays a key role in the reverse cholesterol transport pathway. The purpose of this study was to investigate the association of CETP gene polymorphism with the plasma lipid levels and coronary artery disease (CAD) in Korean men. SUBJECTS AND METHODS: Two hundred and sixteen healthy control subjects (46.8+/-10.6 y) and 95 patients with CAD (58.2+/-8.8 y) were examined. The genotypes of C-629A, Taq1B and I405V were determined by the SNP-IT assay. RESULTS: The allele frequencies of the C:A in the C-629A, B1:B2 in the Taq1B and I:V in the I405V in the control group were 0.51:0.49, 0.63:0.37 and 0.55:0.45, respectively. The genotype distributions of the C-629 A and Taq1B polymorphisms in the CAD patients did not differ from those in the control group. No variation in the CETP genotype was associated with disease progression in the CAD group. The HDL cholesterol in -629A homozygous and Taq1B B2 homozygous were higher than those of the other genotypes. The Taq1B B2 carrier was an independent determinant for HDL cholesterol in the control group. However, I405V polymorphism was not associated with HDL cholesterol. The V allele in the I405V polymorphism was associated with reduced CAD events after controlling the age, BMI and other risk factors (OR:0.4, p<0.01). CONCLUSION: The frequencies of Taq1B and C-629A variants between the healthy and CAD groups did not differ. The B2 carrier in the Taq1B polymorphism was associated with a higher HDL cholesterol concentration. The V variation in the I405V polymorphism had a protective effect against the development of CAD in Korean men.
Alleles ; Cholesterol ; Cholesterol Ester Transfer Proteins* ; Cholesterol, HDL ; Coronary Artery Disease* ; Coronary Disease ; Coronary Vessels* ; Disease Progression ; Gene Frequency ; Genotype ; Humans ; Male ; Plasma ; Risk Factors

A 32-year-old female patient and her sister show high levels of high density lipoprotein (HDL) cholesterol in regular health checkups, since female patient was 11 years old. The patient's serum total cholesterol was 285 mg/dL and HDL cholesterol was 113 mg/dL. Her sister's total cholesterol was 240 mg/dL and the HDL cholesterol measured to be 90 mg/dL. Lipoprotein pattern and cholesteryl ester transfer activity gene analysis were examined in these patients. We found c.1321+1G>A (IVS14+1G/A) hetero mutation in cholesteryl ester transfer protein (CETP) genes. Generally, CETP mediates transfer and exchange of triglycerides and cholesteryl ester between plasma lipoproteins. Also we investigated a key role of HDL-CE and Apo A-1 metabolism. Patients with low levels of CETP have increased serum HDL levels. We hereby report two Korean cases of CETP deficiency in a family. Brief literature review ensues with the cases.
Adult ; Apolipoprotein A-I ; Cholesterol ; Cholesterol Ester Transfer Proteins ; Cholesterol, HDL ; Female ; Humans ; Hypercholesterolemia ; Lipid Metabolism, Inborn Errors ; Lipoproteins ; Plasma ; Protein Deficiency ; Siblings ; Triglycerides

OBJECTIVES: The aim of this study was to examine the associations of cholesterol ester transfer protein (CETP) rs6499861 and rs12708980 with high-density lipoprotein cholesterol (HDL-C) considering obesity and family history of diabetes (FHD) in Korean men and women. METHODS: We analyzed the association of CETP single nucleotide polymorphisms (SNPs) with HDL-C among individuals selected from a hospital (n=4 294) and the Bundang-gu area in Korea (n=2 304). RESULTS: We found that the CETP SNP rs6499861 was associated with a lower HDL-C level (effect per allele: −2.044 mg/dL, p<0.0001). Individuals with a rs6499861 CG/GG genotype had a 1.45-fold higher risk of an abnormal level of HDL-C (<40 mg/dL) than those with a CC genotype. This genotype-HDL-C association was stronger in women (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.39–2.85) compared with men (OR, 1.33; 95% CI, 1.10–1.61) and in women with a FHD (OR, 4.82; 95% CI, 1.86–12.5; p=0.0012) compared with women without a family history. Relative to individuals with a CC genotype and body mass index (BMI) <25.69 kg/m², individuals with a CG/GG genotype and BMI ≥25.69 kg/m² had an OR (95% CI) of 2.61 (1.97–3.47). CONCLUSIONS: These findings indicate that CETP variants are linked to HDL-C level in Koreans and that this link is stronger in obese men and in women who have a FHD.
Alleles ; Body Mass Index ; Cholesterol ; Cholesterol Ester Transfer Proteins ; Cholesterol, HDL ; Female ; Genotype ; Humans ; Korea ; Lipoproteins ; Male ; Motor Activity ; Obesity ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide

OBJECTIVETo analyze the effects of cholesterol ester transfer protein (CETP) Taq1B polymorphism on the response of serum HDL-C to dietary factors in hyperlipidemia patients.

METHODSAll 141 hyperlipidemia residents in a community in Shanghai were investigated by a 3-day diet questionnaire. The serum lipids were analyzed, and the polymorphism of CETP gene was detected by PCR-RFLP method. The correlation between dietary factors and serum HDL-C in different genotype was analyzed when considering the effects of sex, age and body mass index.

RESULTThe HDL-C of hyperlipidemia patients was affected by dietary factors and CETP gene Taq1B polymorphism. The strength of the correlation between dietary factors and serum HDL-C was different among the genotype groups. The relation was shown closer in B(2)B(2) subjects than in B(1)B(1).

CONCLUSIONThe Taq1B CETP gene polymorphism should be a strong determinant of HDL-C in hyperlipidemia patients, and might contribute to the heterogeneity in HDL-C response to dietary intervention.

Cholesterol Ester Transfer Proteins ; genetics ; Cholesterol, HDL ; blood ; Diet ; Disease Susceptibility ; Female ; Gene Frequency ; Genotype ; Humans ; Hyperlipidemias ; blood ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

Recent clinical trials and meta-analyses have indicated that high-intensive statin treatment lowers low-density lipoprotein cholesterol (LDL-C) levels and reduces the risk of nonfatal cardiovascular (CV) events compared with moderate-intensity statin treatment. However, there are residual risks of CV events and safety concerns associated with high-intensity statin treatment. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) study showed that ezetimibe plus moderate-intensity statin therapy after acute coronary syndromes incrementally lowers LDL-C levels and improved CV outcomes compared with moderate-intensity statin therapy. However, despite the LDL-C-lowering effects, a substantial residual CV risk still remains, which includes other lipid abnormalities such as low high-density lipoprotein cholesterol (HDL-C). The most representative agents that primarily increase HDL-C are cholesteryl ester transfer protein (CETP) inhibitors. Until now, 4 CETP inhibitors, including torcetrapib, dalcetrapib, evacetrapib, and anacetrapib, have been introduced and all have significantly raised the HDL-C from 30% to 133%. However, the results for CV outcomes in clinical trials differed, based on the 4 agents. Torcetrapib increased the risk of CV events and total mortality in patients at high CV risk (ILLUMINATE trial). Dalcetrapib and evacetrapib did not result in lower rate of CV events in patients with recent acute coronary syndrome and high risk vascular disease, respectively (dal-OUTCOMES and ACCELERATE trials). However, anacetrapib significantly decreased the incidence of major coronary events in patients with atherosclerotic vascular disease (REVEAL trial). This topic summarizes the major results of recent statin and CETP inhibitor trials and provides framework to interpret and implement the trial results in real clinical practice.
Acute Coronary Syndrome ; Cholesterol ; Cholesterol Ester Transfer Proteins ; Dyslipidemias ; Ezetimibe ; Ezetimibe, Simvastatin Drug Combination ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Incidence ; Lipoproteins ; Mortality ; Vascular Diseases

OBJECTIVETo detect cholesteryl ester transfer protein (CETP) levels, frequencies of CETP D442G and I 14A mutations and characteristics of abnormal lipids in patients with cardio-cerebro vascular diseases.

METHODSNinety-four myocardial infarction (MI) patients, 110 stroke patients and 335 healthy controls were selected. The CETP concentration was determined using ELISA. The CETP activity was measured using a substrate of (14)C-radiolabeled discoidal bilayer particles. The CETP gene mutations were detected by PCR-RFLP.

RESULTSThe CETP concentrations in the MI and stroke group, were higher than those in the controls. The gene mutation frequencies of D442G in the MI, stroke and control group were 3.5%, 3.6% and 5%, respectively, and the frequencies of I 14A were 1.05%, 0.91% and 1%, respectively. One case of D442G homozygote was detected in the healthy group. The frequency of two CETP gene mutations showed no significant difference among the patients and controls. The CETP concentration and activity in subjects with CETP mutations were one-third of those in the control group. The level of HDL-C, apo-A1 increased in the mutation subjects, while the TG level decreased.

CONCLUSIONSThe CETP level increased significantly in patients with cardio-cerebrovascular diseases. The carriers of CETP deficiency had CETP and lipid abnormalities.

Carrier Proteins ; blood ; genetics ; Cholesterol Ester Transfer Proteins ; Glycoproteins ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Mutation ; Myocardial Infarction ; blood ; genetics ; Stroke ; blood ; genetics

OBJECTIVETo study the distribution of cholesteryl ester transfer protein (CETP)-TaqIB polymorphism and plasma concentration in general population and the association between the two.

METHODSA cross-sectional study was carried out in a general population of Beijing in 1999, using stratified-random sampling method. CETP-TaqIB polymorphism and plasma CETP concentration were determined in 719 individual aged 45 - 64 years.

RESULTS(1) Frequencies of B1B1, B1B2 and B2B2 genotypes were 0.356, 0.478 and 0.166, respectively. The frequency of allele B2 was 0.405. Distributions of genotypes and alleles were homogeneous in both sexes. (2) Plasma CETP concentration manifested as a normal distribution, with the mean of 2.03 micro g/ml. The value of female was 20.3%, higher than that of male (P < 0.001). There were no differences among age groups. (3) Plasma CETP concentrations of B1B1 and B1B2 were 19.6% and 13.4% higher than that of B2B2 homozygotes. (4) Stratified by lipid levels, smoking and alcohol consumption, only when tryglyceride exceeded 150 mg/dl, with no significant difference among three genotypes. The effect of lipids, smoking and alcohol consumption status was more significant in B1B2 heterozygotes.

CONCLUSIONCETP-TaqIB polymorphism was a determinant of plasma CETP concentration. However, the effect could be modified by other factors, such as lipids, smoking and alcohol consumption.

Carrier Proteins ; blood ; genetics ; Cholesterol Ester Transfer Proteins ; Cross-Sectional Studies ; Female ; Genotype ; Glycoproteins ; blood ; genetics ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Polymorphism, Genetic ; Sampling Studies

OBJECTIVETo study the correlation between the serum levels of phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), and Chinese medical syndrome types of coronary heart disease (CHD) patients, thus probing a new pathway for the objectivity of CHD syndrome typing and developing therapeutic drugs.

METHODS201 patients with CHD confirmed by coronary angiography were selected. The comprehensive analysis database by the four examination methods was established using generally accepted standard for Chinese medical syndrome typing. Twenty healthy subjects were randomly recruited as the control group. Serum samples were separated from venous blood. The serum activities of PLTP and CETP were assayed by ELISA. The triglyceride (TG) content was determined using acetic acetone coloring method. Contents of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined using precipitation floating enzyme couplet method.

RESULTSSerum levels of PLTP, CETP, and TC of CHD patients of all Chinese medical syndrome types were significantly higher than those of the control group, showing statistical difference (P<0.05, P<0.01). Statistical difference existed in serum levels of TG, HDL-C, and LDL-C of all Chinese medical syndrome types when compared with the control group (P<0.05, P<0.01). Statistical difference existed in serum levels of PLTP between the sthenia in superficiality groups of all Chinese medical syndrome types and the asthenia in origin groups of all Chinese medical syndrome types (P< 0.05). Statistical difference existed in serum levels of TG, HDL-C, and LDL-C between the sthenia in superficiality groups of all Chinese medical syndrome types and the asthenia in origin groups of all Chinese medical syndrome types (P<0.05, P<0.01).

CONCLUSIONSThe serum PLTP levels of CHD patients of sthenia in superficiality significantly increased. Changes in serum lipids was more significant in CHD patients of the sthenia in superficiality syndrome than in those of the asthenia in origin syndrome.

Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Cholesterol ; blood ; Cholesterol Ester Transfer Proteins ; blood ; Coronary Disease ; blood ; diagnosis ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phospholipid Transfer Proteins ; blood ; Triglycerides ; blood