Serum Cholesteryl Ester Transfer Protein Research Articles

Serum Cholesteryl Ester Transfer Protein (CETP) and Sortilin (SORT) in Patients with Psoriasis with Relation to Systemic Treatment.

Psoriasis is a common inflammatory skin disease, which is tightly associated with metabolic disorders. Cholesteryl ester transfer protein (CETP) and sortilin (SORT) are molecules engaged in lipid metabolism of proatherogenic properties. They have been hardly ever studied in psoriasis before. Serum CETP and SORT concentrations were measured in 33 patients with plaque-type psoriasis before and after 12 weeks of treatment with methotrexate or acitretin. There was no significant difference in CEPT and SORT serum concentrations between patients and controls. Positive correlations between CETP after the treatment with acitretin and activity of transaminases (R = 0.65, R = 0.56, respectively) were noted. CETP was positively related with triglycerides (R = 0.49), glucose (R = 0.54) and CRP (R = 0.64) before the treatment with methotrexate, which all disappeared afterwards. Systemic therapy with methotrexate caused normalization of SORT concentration. There was significant correlation between SORT and WBC (p < 0.01) and CRP (p < 0.05). CETP and SORT cannot be used as individual biomarkers. Nevertheless, they show some interesting relations with other parameters. Increased concentration of CETP perhaps could investigated as a marker of liver side effects of acitretin treatment in psoriatics. SORT could be considered as a new indicator of metabolically induced inflammation in psoriasis. Methotrexate may be preferred in patients with high SORT concentrations. Further studies are needed to establish their exact role in psoriatic patients.

High Level of Serum Cholesteryl Ester Transfer Protein and Chemerin as a Risk Factor of Metabolic Syndrome in Adolescent Obese and the Description of Cholesteryl Ester Transfer Protein −629c/A Gene Promoter Polymorphism

BACKGROUND: The prevalence of metabolic syndrome (MS) in children and adolescents has increased, along with increasing incidence of obesity.&#x0D; AIM: The aim of this study was to find out the polymorphism characteristic of cholesteryl ester transfer protein (CETP) -629C/A gene promoter and to prove that the CETP -629C/A polymorphism, serum CETP, and chemerin levels were risk factors of MS in obese adolescents.&#x0D; MATERIALS AND METHODS: A matched case–control study with obese adolescent aged 11–18 years was conducted from May to December 2017. Samples were consecutively recruited in seven junior and senior high schools in Denpasar. Case groups were obese adolescents with MS and control groups were obese adolescents without MS (non-MS obese). Both groups fulfilled eligibility criteria were matched by gender and puberty status. The study data were analyzed by Chi-square test and logistic regression with significant level p &lt; 0.05.&#x0D; RESULTS: Analysis of CETP -629C/A polymorphism showed, AA and CA genotype were not a risk factors for MS when compared with CC genotype (OR = 0.81 [95% CI 0.23–2.88], p = 0.75 and OR = 0.95 [95% CI 0.38–2.37] p = 0.91, respectively). There was no significant difference between individual carriers A allele with individual carriers C allele to risk of MS (OR = 0.91 [95% CI 0.39–2.14], p = 0.83). The cutoff point of CETP levels was ≥2 μg/mL considered as CETP high levels, and &lt;2 μg/mL considered normal; chemerin levels ≥170 ηg/mL considered as chemerin high levels, and &lt;170 ηg/mL considered as normal. High levels of serum CETP were a risk factor in MS compared to normal levels (OR = 2.82 [95% CI 1.07–7.41], p = 0.036) and high levels of serum chemerin were a risk factor in MS compared to normal level (OR = 2.77 [95% CI 1.04–7.40], p = 0.042).&#x0D; CONCLUSION: This study concluded that high levels of serum CETP and chemerin were the risk factors for MS, while genotype AA CETP -629C/A gene polymorphism was not a risk factor for MS.

Calcitriol modulates cholesteryl ester transfer protein (CETP) levels and lipid profile in hypercholesterolemic male rabbits: A pilot study.

Vitamin D3 efficacy against cardiovascular disease prevention has been reported in many experimental studies. We aimed to investigate the effect of the calcitriol or active form of Vitamin D3 (1, 25(OH) 2D3) on serum cholesteryl ester transfer protein (CETP) levels in a rabbit model of atherosclerosis. New Zealand white male rabbits were fed with 1% cholesterol diet and randomly assigned into two groups (n=6). The case group was administrated with 50000 calcitriol (IU/kg/per wk) and the control group which administrated with calcitriol solvent (sesame oil) for 2 months. Then, after two months the lipid profile, CETP and 25OHD3 levels were measured. The serum concentration of CETP was increased after treatment with calcitriol in case group as compared to the control group (41.75±3.19 vs. 34.5±2.3, ng/ml, P<0.05). We also observed higher levels of the 25OHD3 in the calcitriol group at the 1st month (16.3±1.64 vs. 12.8±1.33ng/ml) and the 2nd month (19.5±2.14 vs. 12.5±1.25ng/ml) as compared with the control group. the significant increase in the level of HDL-C was observed in the case group than the control group (P<0.01). In addition, serum levels of LDL- Cholesterol (LDL-C), Triglyceride (TG) were reduced after assessment at 1st and 2nd month after administration of calcitriol. Our research indicated the significant anti-atherogenic effects of calcitriol in the rabbit model of atherosclerosis. However, increased in CETP levels by calcitriol may know as an additional way, which interfere with the anti-atherogenic effects of calcitriol.

Correlation of serum cholestryl ester transfer protein (CETP) level with lipid profile in young myocardial infarction patients

Correlation of serum cholestryl ester transfer protein (CETP) level with lipid profile in young myocardial infarction patients - IJCBR- Print ISSN No: - 2394-6369 Online ISSN No:- 2394-6377 Article DOI No:- 10.18231/j.ijcbr.2019.079, International Journal of Clinical Biochemistry and Research-Int J Clin Biochem Res

Dyslipidemia induced inflammatory status, platelet activation and endothelial dysfunction in rabbits: Protective role of 10-Dehydrogingerdione

10-Dehydrogingerdione is a novel cholesteryl ester transfer protein (CETP) inhibitor of natural origin. Some synthetic CETP inhibitors have recently been reported to suppress proprotein convertase subtilisin/kexin type 9 (PCSK9). Therefore, the present study aimed mainly to clarify the effect of 10-Dehydrogingerdione on cellular adhesion inflammatory molecules, platelet activation and endothelial dysfunction markers in addition to PCSK9 as compared to atorvastatin in dyslipidemic rabbits. Dyslipidemia was induced in 30 male rabbits, distributed in 3 equal groups through feeding dietary cholesterol (0.5% w/w) for 3 months. Two dyslipidemic groups were concurrently treated with either atorvastatin or 10-Dehydrogingerdione (10 mg/kg/ day, p.o) and dietary cholesterol. One additional group including 10 normal rabbits fed normal diet served as normal control (NC) group. Both 10-Dehydrogingerdione and atorvastatin significantly reduced serum CETP level and activity as well as PCSK9 and low density lipoprotein cholesterol (LDL-C) levels but increased high density lipoprotein cholesterol (HDL-C) levels as compared to dyslipidemic control (DC) rabbits (p < 0.001). Both treatments also induced a marked decrease in the interferon-gamma (IFN-γ), soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) levels, inflammatory cell infiltration, as well as atherogenic and coronary risk indexes in addition to aortic atheromatous changes and intima/media ratio, respectively as compared to the DC group (p < 0.001). The reduction in these markers showed a significant correlation with PCSK9 suppression and CETP inhibitory effect. Interestingly, 10-Dehydrogingerdione exerted a greater ameliorative potential regarding these biomarkers than atorvastatin. Our findings suggest that 10-Dehydrogingerdione is a promising PCSK9 inhibitor with a significant protective value against many atherosclerotic risk factors.

Mendelian randomization reveals unexpected effects of CETP on the lipoprotein profile.

According to the current dogma, cholesteryl ester transfer protein (CETP) decreases high-density lipoprotein (HDL)-cholesterol (C) and increases low-density lipoprotein (LDL)-C. However, detailed insight into the effects of CETP on lipoprotein subclasses is lacking. Therefore, we used a Mendelian randomization approach based on a genetic score for serum CETP concentration (rs247616, rs12720922 and rs1968905) to estimate causal effects per unit (µg/mL) increase in CETP on 159 standardized metabolic biomarkers, primarily lipoprotein subclasses. Metabolic biomarkers were measured by nuclear magnetic resonance (NMR) in 5672 participants of the Netherlands Epidemiology of Obesity (NEO) study. Higher CETP concentrations were associated with less large HDL (largest effect XL-HDL-C, P = 6 × 10-22) and more small VLDL components (largest effect S-VLDL cholesteryl esters, P = 6 × 10-6). No causal effects were observed with LDL subclasses. All these effects were replicated in an independent cohort from European ancestry (MAGNETIC NMR GWAS; n ~20,000). Additionally, we assessed observational associations between ELISA-measured CETP concentration and metabolic measures. In contrast to results from Mendelian randomization, observationally, CETP concentration predominantly associated with more VLDL, IDL and LDL components. Our results show that CETP is an important causal determinant of HDL and VLDL concentration and composition, which may imply that the CETP inhibitor anacetrapib decreased cardiovascular disease risk through specific reduction of small VLDL rather than LDL. The contrast between genetic and observational associations might be explained by a high capacity of VLDL, IDL and LDL subclasses to carry CETP, thereby concealing causal effects on HDL.

Biomarkers and Gene Polymorphisms in Members of Long- and Short-lived Families: A Longevity Study.

Background:The influence of biomarkers in human lifespan has been investigated but with no clear results yet.Materials and methods:Lipids, Uric Acid (UA), Adiponectin (ADIPOQ), Insulin-like Growth Factor (IGF-1), cholesteryl ester transfer protein (CETP) and angiotensin-converting enzyme (ACE) proteins, as well as CETP, ADIPOQ, insulin-like growth factor binding protein-3 (IGFBP3) and ACE-gene polymorphisms were evaluated in 149 Greek individuals. The Long-Lived Families (LON) (n=84) comprised of 3 generations: long-lived aged ≥90 years (P), offspring (FL1) and their grandchildren (FL2), while the Short-Lived Families (EAD) (n=65) where both parents died <75 years, comprised of 2 generations: middle-aged (FD1) and children (FD2).Results:Serum CETP and IGF-1 levels were lower, whereas AdipoQ concentrations were higher in P compared with FL1 and FL2 members (CETP: p = 0.03 for both comparisons; IGF-1 p < 0.001 for both comparisons and ADIPOQ: p = 0.001 and p = 0.004, respectively). Furthermore, serum triglycerides, UA and glucose concentrations were higher in FD1 compared with FD2 subjects (p=0.001, 0.02 and ≤0.001, respectively). In FD2 and FL2, CETP levels were lower in individuals with B2B2 compared with B1B1 genotype (p=0.007). Additionally, ACE concentrations were higher in individuals with DD compared with II genotype in both Families (p=0.001). After adjustment for age and gender, CETP levels were lower in P and FL2 individuals with B2B2 compared with the B1B1 genotype (p=0.004 and 0.007, respectively).Conclusion:Increase serum TGs, UA and GL concentrations were higher in the middle-aged individuals compared with their children in families independently of their lifespan. The serum adiponectin concentration was the highest in the oldest old individuals implying beneficial influence on lifespan. Independently of family’s lifespan history, the youngest individuals with CETPB2B2 genotype, compared with individuals with CETPB1B1 genotypes, had lower serum CETP concentrations. The knowledge of the unfavourable gene(s)influencing human lifespan may be helpful in encouraging individuals to follow healthier lifestyle habits and better control their high-risk biomarkers.

The effects of curcumin and a modified curcumin formulation on serum Cholesteryl Ester Transfer Protein concentrations in patients with metabolic syndrome: A randomized, placebo-controlled clinical trial

Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl ester from HDL-C to LDL-C and VLDL-C. The aim of the present trial was to evaluate the effect of curcumin and its modified formulation on serum CETP concentrations in patients with metabolic syndrome. Participants were randomly allocated to one of three groups of40 subjects receiving either unmodified curcumin or its phospholipid complex or placebo. Lipid profile and plasma CETP were measured at the start and six weeks after initiation of the treatment. The normality of data distribution was assessed by Kolmogorov-Smirnov test. Wilcoxon test was used for comparing the data before and after the intervention. The percent changes of CETP and biochemical factors among the three groups were compared using Kruskal-Wallis test. Serum CETP levels were not significantly altered among patients receiving curcumin. Curcumin and its complex had no significant effect on serum CETP concentrations.

Blood Pressure Lowering Effect of Cuban Policosanol is Accompanied by Improvement of Hepatic Inflammation, Lipoprotein Profile, and HDL Quality in Spontaneously Hypertensive Rats.

We investigated the antihypertensive effect of policosanol on spontaneously hypertensive rats (SHR). For this, we analyzed blood pressure, blood lipid, and lipoprotein properties in male SHR after consumption of Cuban policosanol (PCO). The experimental groups were as follows: normotensive Wistar Kyoto (WKY) control, SHR group fed normal diet (ND), SHR group fed 20 mg of PCO, SHR group fed 100 mg of PCO, and SHR group fed 200 mg of PCO per kg of body weight. After eight weeks, the SHR control group showed gradual increases up to 22% in systolic blood pressure (SBP) and 17.6% in the diastolic blood pressure (DBP) compared with values at week 0. However, policosanol consumption had a dose-dependent reduction effect on SBP and also reduced DBP up to 16% in a dose-dependent manner. Heart rate (HR) bpm increased by six percent in the SHR control, whereas the 20 mg, 100 mg, and 200 mg of policosanol groups showed a reduction of 36%, 28%, and 34% respectively. Although serum total cholesterol (TC) level of SHR was not affected by policosanol consumption (70–80 mg/dL), serum triglyceride (TG) level significantly decreased in the SHR + 200 mg of PCO group. Serum high-density lipoprotein cholesterol (HDL-C) level was also significantly elevated by policosanol consumption. The % HDL-C/TC ratio was elevated in the policosanol group up to 67–70%, whereas the SHR control group showed a ratio of 58%. Serum cholesteryl ester transfer protein (CETP) activity was reduced by policosanol in a dose-dependent manner. Although the serum glutamate oxaloacetate transaminase (GOT)/ glutamate pyruvate transaminase (GPT) were similar across all groups, policosanol consumption caused reduction of reactive oxygen species (ROS) levels in hepatic tissue. The SHR control group showed a 2.1-fold higher serum C-reactive protein (CRP) level than the WKY group, whereas the CRP level decreased in the SHR + 200 mg of PCO group (up to 45%) than SHR control group. Aldosterone level was reduced in the policosanol group (up to 34%) in a dose-dependent manner compared to the control. In conclusion, eight weeks of policosanol consumption in SHR resulted in remarkable reduction of blood pressure, serum aldosterone, and serum TG levels along with the elevation of HDL-C and improvement of hepatic inflammation.

CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease.

We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium). In the discovery analysis (n=4248), we identified 3 independent variants (P<5×10-8) that determine CETP concentration. These single-nucleotide polymorphisms were mapped to CETP and replicated in a separate subpopulation (n=1458). Per-allele increase (SE) in serum CETP was 0.32 (0.02) µg/mL for rs247616-C, 0.35 (0.02) µg/mL for rs12720922-A, and 0.12 (0.02) µg/mL for rs1968905-G. Combined, these 3 variants explained 16.4% of the total variation in CETP concentration. One microgram per milliliter increase in genetically determined CETP concentration strongly decreased high-density lipoprotein cholesterol (-0.23 mmol/L; 95% confidence interval, -0.26 to -0.20), moderately increased low-density lipoprotein cholesterol (0.08 mmol/L; 95% confidence interval, 0.00-0.16), and was associated with an odds ratio of 1.08 (95% confidence interval, 0.94-1.23) for CAD risk. This is the first genome-wide association study identifying independent variants that largely determine CETP concentration. Although high-density lipoprotein cholesterol is not a causal risk factor for CAD, it has been unequivocally demonstrated that low-density lipoprotein cholesterol lowering is proportionally associated with a lower CAD risk. Therefore, the results of our study are fully consistent with the notion that CETP concentration is causally associated with CAD through low-density lipoprotein cholesterol.

The effect of artichoke leaf extract supplementation on lipid and CETP response in metabolic syndrome with respect to Taq 1B CETP polymorphism: A randomized placebo-controlled clinical trial

IntroductionThe potentially favorable effects of artichoke leaf extract (ALE) have been shown on lipid profile; however, results are inconsistent. Taq IB polymorphism in cholesteryl ester transfer protein (CETP) gene may modulate the response to intervention. This study was aimed to examine the effects of ALE supplementation on serum lipid profile and CETP levels regarding CETP Taq IB polymorphism in patients with metabolic syndrome (MetS). MethodsIn this double-blind placebo-controlled clinical trial, 80 patients with MetS were randomized to receive ALE (1800 mg per day as four tablets) or matching placebo for 12 weeks. Serum levels of lipid profile and CETP, as well as physical activity levels were assessed before and after the intervention. Physical activity levels were measured using short form of the International Physical Activity Questionnaire (IPAQ-SF). Moreover, patients were genotyped for CETP Taq IB polymorphism. ResultsMean age and BMI of the patients was 38.91 ± 6.90 years and 34.32 ± 4.28 kg/m2, respectively. Twenty-eight percent of the patients were male. ALE supplementation decreased serum triglyceride (TG) level compared to placebo over 12 weeks (−10% vs. −2%, p = 0.01). There was no interaction between CETP Taq IB genotype and response to ALE supplementation. The subgroup analysis showed that in men carriers of Taq IB-B1B1, LDL-C level significantly decreased in ALE group compared to the placebo group (-15% vs. 9%, p = 0.004). ConclusionsALE supplementation decreased TG levels without intervention-genotype interaction in patients with MetS. However, men with Taq IB-B1B1 genotype indicated a reduction of LDL-C in response to ALE.

Mendelian randomization analysis of cholesteryl ester transfer protein and subclinical atherosclerosis: A population-based study

Several trials to prevent cardiovascular disease by inhibiting cholesteryl ester transfer protein (CETP) have failed, except Randomized EValuation of the Effects of Anacetrapib through Lipid-modification. Thus far, it is unclear to what extent CETP is causally related to measures of atherosclerosis. The aim of the article was to study the causal relationship between genetically determined CETP concentration and carotid intima-media thickness (cIMT) in a population-based cohort study. In the Netherlands Epidemiology of Obesity study, participants were genotyped, and cIMT was measured by ultrasonography. We examined the relation between a weighted genetic risk score for CETP concentration, based on 3 single-nucleotide polymorphisms that have previously been shown to largely determine CETP concentration and cIMT using Mendelian randomization in the total population and in strata by sex, Framingham 10-year risk, (pre)diabetes, high-density lipoprotein cholesterol, triglycerides, and statin use. We analyzed 5655 participants (56% women) with a mean age of 56 (range 44-66) years, body mass index of 26 (range 17-61) kg/m2, and serum CETP of 2.47 (range 0.68-5.33) μg/mL. There was no evidence for a causal relation between genetically determined CETP and cIMT in the total population, but associations were differently directed in men (16μm per μg/mL increase in genetically determined CETP; 95% confidence interval: -8, 39) and women (-8μm; -25, 9). Genetically determined CETP appeared to be associated with cIMT in normoglycemic men (26μm; -1, 52) and in (pre)diabetic women (48μm; -2, 98). In this population-based study, there was no causal relation between genetically determined CETP concentration and cIMT in the total population although we observed directionally differing effects in men and women. Stratified results suggested associations in individuals with different cardiometabolic risk factor profiles, which require replication.

Serum Lipid Transfer Proteins in Hypothyreotic Patients Are Inversely Correlated with Thyroid-Stimulating Hormone (TSH) Levels.

BackgroundPlasma cholesteryl ester transfer protein (CETP) activity is often decreased in patients with hypothyroidism, whereas less is known about the phospholipid transfer protein (PLTP). We aimed to evaluate simultaneously serum CETP and PLTP activity in patients diagnosed with hypothyroidism.Material/MethodsThe selection criteria for control group members (without thyroid dysfunction) in this case to case study were levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides similar to those in study group patients (101 patients diagnosed with hypothyroidism). Serum CETP and PLTP activities were measured by homogenous fluorometric assays using synthetic donor particle substrates.ResultsSerum CETP and PLTP activities in hypothyreotic patients were lower (p<0.001) compared with those in healthy subjects. This lowering was associated with significant changes in HDL-C subclasses: decrease in HDL2- and increase in HDL3 cholesterol levels. Multiple linear regression analyses adjusted for age, sex, body mass index, smoking habits, and alcohol drinking showed a strong association between hypothyroidism and activity of lipid transfer proteins. A linear inverse relationship between thyroid-stimulating hormone (TSH) and CETP (r=−0.21; p<0.01) and between TSH and PLTP (r=−0.24; p<0.001) was shown. There also was a positive correlation (p<0.001) between CETP and HDL2 cholesterol (r=0.27) and between PLTP and HDL2 cholesterol (r=0.37). A negative correlation between CETP and HDL3 cholesterol (r=−0.22: p<0.01) and between PLTP and HDL3 cholesterol (r=−0.24; p<0.001) has been demonstrated as well.ConclusionsThe decreased HDL2 and increased HDL3 cholesterol levels in subjects with hypothyroidism are consequences of decreased activity of lipid transfer proteins. These changes are early symptoms of lipid disturbances in hypothyroidism.

Cholesteryl Ester Transfer Protein Intimately Involved in Dyslipidemia-Related Susceptibility toCognitive Deficits in Type 2 Diabetic Patients.

Cholesteryl ester transfer protein (CETP) is involved in diabetic dyslipidemia. We aim to test the hypothesis that CETP might be of importance in mediating dyslipidemia-related susceptibility to cognitive deficits in diabetic patients. We recruited 190 type 2 diabetic patients and divided them into two groups according to the Montreal Cognitive Assessment (MoCA) score. The association between CETP and cognitive decline was analyzed with logistic regression and stratification. There were 110 diabetic patients with mild cognition impairment (MCI) and 80 healthy cognition subjects as controls. Dyslipidemia is more common among diabetic patients with MCI; they had a significant increase of serum CETP concentrations, which was negatively correlated with MoCA (r = -0.638; p < 0.001). Negative correlations were also found between the serum CETP concentration with the Auditory Verbal Learning Test (r = -0.266; p = 0.008), indicating memory deficit. Logistic regression analysis revealed that CETP concentration was an independent factor of diabetic MCI (p < 0.001). Further stratification study showed that high serum levels of CETP was an independent risk factor of MCI in diabetic patients with a low density lipoproteins level ≥2.59 mmol/L, or high density lipoproteins level ≤1.0 mmol/L for men and ≤1.3 mmol/L for women, or TG level ≥1.7 mmol/L, after adjusting for age, sex, education, and glucose control (all ps < 0.05). CETP was intimately involved in dyslipidemia-related susceptibility to cognitive decline, especially memory function in type 2 diabetic patients.

Association of Cholesteryl Ester Transfer Protein (CETP) Gene -629C/A Polymorphism with Angiographically Proven Atherosclerosis

Association of cholesteryl ester transfer protein (CETP) Gene -629C/A Polymorphism with angiographically proven atherosclerosis CETP gene has been linked to CAD risk via its role in HDL and LDL metabolism. There is no agreement of whether CETP is atherogenic or not. Furthermore, various genotypes of CETP gene have been associated with CETP levels and thus with atherosclerosis risk. Our aim was to study the association of CETP -629C/A gene polymorphism with CETP and HDL levels and their association if any with atherosclerosis. Study population consisted of angiographically documented 50 cases with coronary artery atherosclerosis and 50 controls negative for atherosclerosis of coronary artery. Serum lipid profile was measured on SYNCHRON CX-9 using standard kits. Serum CETP levels were measured by ELISA method. CETP -629C/A gene polymorphism was studied using PCR-RFLP method. There was no significant difference in lipid profile of the two groups. However, serum CETP level was significantly higher (46.44±21.75ng/ml) in cases than controls (37.10±21.92ng/ml) with p value =0.035. The frequency of -629A allele was higher (0.85) in cases than that of controls (0.81). Homozygosity of A allele was more in subjects with atherosclerosis of coronary artery. We conclude that CETP is atherogenic and could be used as atherogenic risk predictor in angiographically proven atherosclerosis. Also A allele of -629C/A polymorphism is more prevalent in cases; indicating its effect on expression of CETP gene.

Serum CETP concentration is not associated with measures of body fat: The NEO study

IntroductionAdipose tissue has been postulated to contribute substantially to the serum cholesteryl ester transfer protein (CETP) pool. However, in a recent large cohort study waist circumference was not associated with plasma CETP. The aim of the present study was to further examine associations of accurate measures of body fat and body fat distribution with serum CETP concentration. MethodsIn this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, we examined in 6606 participants (aged 45–65 years) the associations of total body fat, body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), abdominal subcutaneous (aSAT) and visceral adipose tissue (VAT) assessed with magnetic resonance imaging (n = 2547) and total and trunk fat mass assessed with dual-energy X-ray absorptiometry (n = 909) with serum CETP concentration. Regression models were adjusted for age, ethnicity, sex, dietary intake of fat and cholesterol, physical activity, smoking and menopausal status. ResultsMean (SD) age was 56 (6) years and BMI 26.3 (4.4) kg/m2, 56% were women. Mean serum CETP concentration was 2.47 μg/mL. The difference in serum CETP was 0.02 μg/mL (95%CI: −0.01, 0.05) per SD total body fat (8.7%), and 0.02 μg/mL (0.00, 0.04) per SD BMI (4.4 kg/m2). Similar associations around the null were observed for waist circumference, WHR, aSAT, VAT, total and trunk fat mass. ConclusionIn this population-based study, there was no evidence for clinically relevant associations between several measures of body fat and serum CETP concentration. This finding implies that adipose tissue does not contribute to the CETP pool in serum.

Serum CETP and PLTP activity in middle-aged men living in urban or rural area of the Lower Silesia region. PURE Poland sub-study.

IntroductionThe dependence of lipid transfer proteins on significant pro-atherogenic factors is unclear. The aim of the study was to evaluate serum cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activity in relation to lipid disturbances in men living in an urban or rural area.Material and methodsA group of 427 men, volunteers for the Prospective Urban Rural Epidemiology (PURE) sub-study – 263 urban inhabitants (aged 51.9 ±6.0) and 164 residents of villages (aged 51.1 ±5.9) – were examined. In the multivariable linear regression model, the following factors were included as potential confounders: age, body mass index (BMI), smoking, alcohol consumption, hs-C-reactive protein reaction (hs-CRP) and co-existence of chronic diseases.ResultsIn multiple linear regression models, site of residence (urban or rural area) was the most important independent and consistent predictor of CETP and PLTP activity; β coefficients (95% CI) for CETP (0.18) and PLTP (–0.29) were significant at levels of p < 0.001. Three-way analysis of variance showed no effect of smoking or moderate alcohol consumption on lipid transfer proteins; however, CETP activity showed an interaction effect between these risk factors. In the group of all men, CETP activity was significantly and positively correlated with total cholesterol (r = 0.24), low-density lipoprotein cholesterol (r = 0.18), and non-high density lipoprotein cholesterol (r = 0.21), whereas PLTP activity was correlated with BMI (r = 0.12). Body mass index in rural men was higher than in the urban male population.ConclusionsIncreased PLTP activity, recognized as a pro-atherogenic factor, and decreased CETP activity, known as a protective factor, both observed in men living in rural areas, are probably conditioned by nutritional and/or genetic factors.

High level of serum cholesteryl ester transfer protein in active hepatitis C virus infection.

To determine the significance of cholesteryl ester transfer protein (CETP) in lipoprotein abnormalities in chronic hepatitis C virus (HCV) infection. We evaluated the significance of the serum concentration of CETP in 110 Japanese patients with chronic HCV infection. Fifty-five patients had active HCV infection, and HCV eradication had been achieved in 55. The role of CETP in serum lipoprotein abnormalities, specifically, in triglyceride (TG) concentrations in the four major classes of lipoproteins, was investigated using Pearson correlations in conjunction with multiple regression analysis and compared them between those with active HCV infection and those in whom eradication had been achieved. The serum CETP levels of patients with active HCV infection were significantly higher than those of patients in whom HCV eradication was achieved (mean ± SD, 2.84 ± 0.69 μg/mL vs 2.40 ± 1.00 μg/mL, P = 0.008). In multiple regression analysis, HCV infection status (active or eradicated) was an independent factor significantly associated with the serum CETP level. TG concentrations in low-density lipoprotein (mean ± SD, 36.25 ± 15.28 μg/mL vs 28.14 ± 9.94 μg/mL, P = 0.001) and high-density lipoprotein (HDL) (mean ± SD, 25.9 ± 7.34 μg/mL vs 17.17 ± 4.82 μg/mL, P < 0.001) were significantly higher in patients with active HCV infection than in those in whom HCV eradication was achieved. The CETP level was strongly correlated with HDL-TG in patients with active HCV infection (R = 0.557, P < 0.001), whereas CETP was not correlated with HDL-TG in patients in whom HCV eradication was achieved (R = -0.079, P = 0.56). Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.

Enhancement of High-Density Lipoprotein Cholesterol Functions by Encapsulation of Policosanol Exerts Anti-Senescence and Tissue Regeneration Effects Via Improvement of Anti-Glycation, Anti-Apoptosis, and Cholesteryl Ester Transfer Inhibition

Consumption of policosanol (PCO), a refined mixture of sugar cane wax alcohols, can elevate serum levels of high-density lipoprotein cholesterol (HDL-C), although the molecular mechanism is still unknown. To investigate the mechanism of action responsible for the anti-senescence effects of PCO on lipoprotein metabolism and HDL functionality, we synthesized reconstituted HDL (rHDL) containing PCO. Encapsulation of PCO by rHDL (PCO-rHDL) enhanced anti-oxidant activity against cupric ion-mediated low-density lipoprotein (LDL) oxidation. PCO-rHDL (final concentration, 9 μM PCO) showed more potent anti-oxidant activity than vitamin C treatment (final concentration, 100 μM). PCO-rHDL inhibited fructose-mediated glycation, which is a major pathological mechanism of diabetic complications, in a dose-dependent manner. PCO also showed cytoprotective effects in monocytes and macrophages with less triggering of apoptotic processes and reactive oxygen species (ROS) production in the presence of hydrogen peroxide (H2O2). PCO-rHDL strongly inhibited uptake of acetylated LDL into macrophages, which is an initial atherosclerotic process. Surprisingly, PCO-rHDL inhibited human serum cholesteryl ester transfer protein (CETP) activity by up to 47% (final concentration, 10 μM PCO). Subcutaneous injection of PCO-rHDL dose-dependently enhanced tissue regeneration activity by 2.4-fold and 3.6-fold compared to that of the phosphate-buffered saline (PBS) control. In conclusion, PCO in HDL showed potent anti-oxidant, anti-glycation, and CETP inhibitory activities along with tissue regenerative activity, especially upon incorporation into HDL. These results suggest that PCO can enhance functionality of HDL in serum to exert anti-senescence and longevity effects.

The Relationship Between Lipoprotein-Associated Phospholipase A(2), Cholesteryl Ester Transfer Protein and Lipid Profile and Risk of Atherosclerosis in Women with Iron Deficiency Anaemia.

The relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2), cholesteryl ester transfer protein (CETP), and risk of atherosclerosis in IDA women has not been fully clarified. The objective of this study was to investigate lipid-related atherogenic risk factors in women with IDA. Eighty women with IDA and 80 age-matched healthy women as the control group were enrolled in the study. Serum lipid profile, Lp-PLA2, and CETP were determined. Correlations between lipid-related atherogenic risk factors were analyzed by Pearson's correlation analyses. TG levels were higher and HDL-C levels were lower in the IDA women. Lp-PLA2 activity, Lp-PLA2 concentration, and CETP concentration were higher in the IDA women. There were negative correlations between activity or concentration of Lp-PLA2 and hemoglobin level (r = -0.29 or r = -0.33, p < 0.05), as well as HDL-C level (r = -0.38 or r = -0.35, p < 0.05). Positive correlations were observed between Lp-PLA2 activity and Lp-PLA2 concentration and low-density lipoprotein cholesterol (LDL-C) level (r = 0.41 or r = 0.36 respectively, p < 0.05). CETP concentration was negatively correlated with hemoglobin (r = -0.56, p < 0.01) and HDL-C level (r = -0.35, p < 0.05) and positively correlated with triglyceride level (r = 0.34, p < 0.05). Increases in the levels of circulating CETP and Lp-PLA2 might partly play a role in the atherogenic disturbances in patients with IDA through increased susceptibility to lipid peroxidation.