Serum Cholesteryl Ester Transfer Protein Concentrations 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.

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.

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.

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.

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.

Changes in cholesteryl ester transfer protein concentration during normal gestation

Background: It has been shown that endogenous estrogen may affect the concentration of cholesteryl ester transfer protein (CETP) and that the gestation in women is accompanied by increased levels of endogenous estrogen. Objectives: To examine the changes in CETP concentration and to investigate the relationship between CETP and estrogen levels during normal pregnancy. Methods: Serum concentrations of CETP, estrogen and lipid traits were determined from 296 healthy women at different times during gestation. Results: Pregnant women exhibited a significant elevation in the concentration of CETP as compared with non-pregnant women (3.11 ± 1.51 mg/L vs. 2.64 ± 1.25 mg/L, p <0.001). The CETP concentration was highest in the first trimester (3.85 ± 1.33 mg/L, compared with controls, p <0.0001), declined progressively from the first to the third trimester and still remained elevated in the third trimester as compared with non-pregnant subjects (p <0.05). A negative correlation was noted between serum CETP and estradiol (E 2 ) levels in pregnant women (r=-0.288, p <0.0001). In addition, significantly negative correlations between the serum CETP concentration and all the lipid traits examined were found in gestating women. Conclusion: CETP concentrations were significantly elevated in pregnancy and decreased progressively from early to late gestation. The results suggest that endogenous E 2 is either not involved or its effect on CETP is dominated by elevated lipid levels or some other factors during mid and late pregnancy.

Relationship between endogenous estrogen concentrations and serum cholesteryl ester transfer protein concentrations in Chinese women

Background: CETP plays an important role in HDL metabolism and in the reverse cholesterol transport pathway. Methods: The relationship between the changes of endogenous estrogen and the concentration of cholesteryl ester transfer protein (CETP) in the serum of Chinese women was investigated. Serum concentrations of estradiol (E 2), follicle-stimulating hormone (FSH), CETP and lipid profile were determined in 196 Chinese women (52 premenopausal with ages ranging from 18 to 40 years, 57 perimenopausal from 41 to 60 years, and 87 postmenopausal from 61 to 81 years). Results: Serum CETP concentration was significantly lower in postmenopausal women compared with those in perimenopausal and premenopausal women (1.39±1.06, 2.36±1.50 and 2.31±1.25 mg/l, respectively, P<0.0001). Even in the women around the menopausal, CETP concentration in postmenopause was significantly lower than that in premenopause (1.93±1.33 vs. 3.42±1.35 mg/l, P<0.01). In addition, CETP concentration had a highly positive correlation with serum concentration of E 2 ( r=0.243, P<0.001), while negative correlation of CETP concentration with serum concentration of FSH was found ( r=−0.273, P<0.001). Conclusions: Estrogen may affect the concentration of CETP.

Cholesteryl ester transfer protein as a protective factor against vascular disease in hemodialysis patients

Cholesteryl ester transfer protein (CETP) may promote reverse cholesterol transport. An elevated concentration of high-density lipoprotein cholesterol (HDL-C) is a protective factor against atherosclerosis. However, the effects of CETP itself and its interaction with HDL-C have not been investigated in hemodialysis patients, who are at high risk for atherosclerosis and generally considered to have decreased reverse cholesterol transport. We investigated the independent or synergistic influence of postprandial serum CETP and HDL-C concentrations on apparent atherosclerotic complications in 202 hemodialysis patients aged 40 to 80 years. Patients with vascular disease (n = 39) had significantly lower concentrations of CETP than those without vascular disease (n = 163). When all study subjects were divided into four groups according to CETP and HDL-C concentrations based on median values, we found significant differences in the prevalence of vascular disease (test for trend, P < 0.005): 28.8% in group I (HDL-C < 48 mg/dL; CETP <2.2 μg/mL); 25.0% in group II (HDL-C < 48 mg/dL; CETP ≥ 2.2 μg/mL); 17.8% in group III (HDL-C ≥ 48 mg/dL; CETP < 2.2 μg/mL); and 6.9% in group IV (HDL-C ≥ 48 mg/dL; CETP ≥ 2.2 μg/mL). Multiple logistic regression analysis retained the interaction term between HDL-C (in milligrams per deciliter) and CETP (in micrograms per milliliter), but not HDL-C or CETP itself, as inversely associated with vascular disease in the entire patient group. In patients with HDL-C levels at the median value or greater, CETP had an independent odds ratio of 0.31 (95% confidence interval, 0.1 to 0.97; P < 0.05) after adjusting for age. These results suggest that CETP may serve as a protective factor against vascular disease in hemodialysis patients, especially those with normal or elevated HDL-C concentrations. © 2001 by the National Kidney Foundation, Inc.