OBJECTIVE: To explore the correlation of cytochrome B-245 alpha chain (CYBA) rs4673 and cholesteryl ester transfer protein (CETP) rs12720922 polymorphisms with the susceptibility of gene-ralized aggressive periodontitis (GAgP). METHODS: The study was a case-control trial. A total of 372 GAgP patients and 133 periodontally healthy controls were recruited. The CYBA rs4673 and CETP rs12720922 polymorphisms were detected by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Logistic regression models were used to analyze the correlation of CYBA rs4673 and CETP rs12720922 variants with the susceptibility of GAgP. The interaction between the two gene polymorphisms to the susceptibility of GAgP was analyzed by the likelihood ratio test. The interaction model adopted was the multiplication model. RESULTS: The mean age of GAgP group and control group was (27.5±5.2) years and (28.8±7.1) years respectively. There was significant difference in age between the two groups (P < 0.05). The gender distribution (male/female) was 152/220 and 53/80 respectively, and there was no significant difference between GAgP group and controls (P>0.05). For CYBA rs4673, the frequency of CT/TT genotype in the GAgP group was significantly higher than that in the controls [18.0% (66/366) vs. 10.6% (14/132), P < 0.05]. After adjusting age and gender, the individuals with CT/TT genotype had a higher risk of GAgP (OR=1.86, 95%CI: 1.01-3.45, P < 0.05), compared with CC genotype. There was no statistically significant difference in distributions of the CETP rs12720922 genotypes (GG, AA/AG) between GAgP patients and healthy controls (P>0.05). A significant interaction between CYBA rs4673 and CETP rs12720922 in the susceptibility to GAgP was observed. The GAgP risk of the individuals with CYBA rs4673 CT/TT and CETP rs12720922 GG genotypes was significantly increased (OR=3.25, 95%CI: 1.36-7.75, P < 0.01), compared with those carrying CC and AA/AG genotypes. CONCLUSION CYBA rs4673 CT/TT genotype is associated with GAgP susceptibility. There is a significant interaction between CYBA rs4673 CT/TT genotype and CETP rs12720922 GG genotype in the susceptibility of GAgP.
Adult ; Aggressive Periodontitis/genetics* ; Case-Control Studies ; Cholesterol Ester Transfer Proteins/genetics* ; Cytochrome b Group ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; NADPH Oxidases/genetics* ; Polymorphism, Single Nucleotide ; Young Adult

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

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 assess the association between I405V and D442G polymorphisms of the CETP gene with cerebral hemorrhage (CH) and a related lipid profile among ethnic Han Chinese from Changsha.

METHODSA case-control study was carried out, which enrolled 170 cerebral hemorrhage patients and 191 ethnicity-, age- and sex-matched health controls. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine the polymorphisms. Lipid profile was determined by means of oxidase method. Statistic analyses were performed with SPSS 16.0.

RESULTSNo significant difference was found in the CETP gene I405V and D442G genotypes and allelic distribution between the CH patients and controls (P>0.05). There was no association between CETP gene I405V polymorphism and lipid profile in both groups (P>0.05). CH patients with DG genotype of the D442G polymorphism had higher TC and low density lipoprotein-cholesterol (LDL-C) levels than those with a DD genotype(P<0.05).

CONCLUSIONCETP gene I405V polymorphism may not be associated with CH among ethnic Han Chinese from Changsha, while the D442G polymorphism of the CETP gene may be associated with TC and LDL levels in the same population.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Case-Control Studies ; Cerebral Hemorrhage ; blood ; ethnology ; genetics ; China ; ethnology ; Cholesterol Ester Transfer Proteins ; genetics ; metabolism ; Cholesterol, HDL ; blood ; Female ; Humans ; Lipids ; blood ; chemistry ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Polymorphism, Single Nucleotide

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

Although statins have demonstrated consistent and strong effects on cardiovascular prevention, non-statin drugs have failed to show additional clinical benefit. Consequently, statins are currently recommended as first-line therapy in dyslipidemia. On the contrary, non-statin drugs are indicated in limited cases in which statins are not sufficiently effective or intolerable. A recent trial on ezetimibe provides evidence supporting further prescription of this agent. Proprotein convertase subtilisin-kexin type 9 inhibitors have strong low-density lipoprotein-cholesterol-lowering effects and were just approved in Western countries. However, results of clinical outcomes are not yet available. Other non-statin lipid-modifying agents have their own roles and limitations. Thus, it is important to have correct knowledge on these agents for optimal treatment of dyslipidemic patients.
Cholesterol Ester Transfer Proteins ; Dyslipidemias* ; Fatty Acids, Omega-3 ; Fibric Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Niacin ; Prescriptions ; Proprotein Convertases ; Ezetimibe

OBJECTIVETo investigate cholesteryl ester transfer protein (CETP) gene polymorphism -629C/A among Han Chinese patients with coronary heart disease (CHD) in Tianjin region, and to assess the influence of genetic factors on therapeutic effect of atorvastatin and clinical outcome in order to provide a pharmacogenomic basis for personalized treatment.

METHODSFrom October 2010 to July 2011, 232 patients with angiographically confirmed CHD were recruited. Polymorphism of position -629 of CETP gene promoter was determined with polymerase chain reaction - restricted fragment length polymorphism (PCR-RFLP) method. Serum level of CETP was determined with enzyme-linked immunosorbent assay (ELISA). Lipid level in all patients was determined at baseline and after 12 months of treatment with 20 mg/d atorvastatin. Clinical follow-up was carried out for more than a year (12-23 months). Major adverse cardiac events including death, non-fatal infarction, revascularization and stroke (MACE) were recorded. A Kaplan-Meier log-rank test was used to compare MACE-free survival for individuals with various genotypes.

RESULTSThe frequency of -629A allele was 0.408. Compared with CC or CA genotypes, individuals with AA genotype had lower CETP levels and higher high-density lipoprotein cholesterol (HDL-C) levels, albeit without statistical significance (F = 0.893, P = 0.411 and F = 1.279, P = 0.282, respectively). There also appeared to be a negative correlation between serum HDL-C and CETP levels, though no statistical significance was detected (r = -0.151, P = 0.081). After 12 months atorvastatin therapy, individuals with CC genotype had greater reduction of low-density lipoprotein cholesterol (LDL-C), reduced LP(a) and elevated HDL-C compared with CA or AA genotypes. LDL-C level has decreased by 35.41% in CC homozygotes, 18.84% in CA heterozygotes and 8.15% in AA homozygotes (P = 0.001). HDL-C level has increased by 14.37% in CC homozygotes, 10.48% in CA heterozygotes and 6.64% in AA homozygotes, respectively. However, above changes did not reach statistical significance (P = 0.470). The incidence of MACE after a mean follow-up of (18.66 ± 5.99) months was 7.76%, which included 2 (0.86%) deaths, 5 (2.16%) non-fatal infarctions, 9 (3.88%) revascularizations and 2 (0.86%) strokes. The cumulative MACE-free survival rates were 92.4%, 85.3% and 65.0% for CC, CA and AA genotypes, respectively (Log-rank P = 0.444).

CONCLUSIONOur results suggested that AA variant for the -629A allele of CETP gene had higher HDL-C levels and reduced CETP levels, though patients with CC genotype appeared to have better benefited from statin therapy with reduction in LDL-C and LP(a) levels. Long-term clinical prognosis was however not affected by the 3 genotypes.

Adult ; Aged ; Atorvastatin Calcium ; Cholesterol Ester Transfer Proteins ; blood ; genetics ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Artery Disease ; blood ; drug therapy ; genetics ; Female ; Heptanoic Acids ; therapeutic use ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Polymorphism, Single Nucleotide ; Pyrroles ; therapeutic use ; Treatment Outcome

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

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

Although statins reduced cardiovascular mortality, these drugs did not prevent myocardial infarction in some patients. Previous studies showed that genetic variation in cholesteryl ester transfer protein (CETP) gene was linked to this response. The identified gene is characterized by two different variants: B1 and B2 alleles identified by the presence and absence, respectively, of a restriction site for the enzyme Taq1 in intron 1. The present study identified the variation in Taq1B of the gene using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) in 130 patients. An association study of Taq1B with the response of 24 middle-aged dyslipidemic patients to simvastatin treatment for 8 weeks was also done. The overall allele frequencies of B1 and B2 alleles were 0.548 and 0.462, respectively. The genotype frequencies were in Hardy-Weinberg equilibrium. The distinguishing feature of individuals with B1B1 genotype when treated with simvastatin was their rapid increase in high density lipoprotein (HDL) observed after 2 weeks which continued till the 8th week treatment. The expected HDL elevation among individuals with B1B2 genotype was observed only after the 8th week simvastatin treatment.

Human ; Middle Aged ; Alleles ; Cholesterol Ester Transfer Proteins ; Gene Frequency ; Genotype ; Hydroxymethylglutaryl-coa Reductase Inhibitors ; Introns ; Lipoproteins, Hdl ; Myocardial Infarction ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Simvastatin