Objective: To investigate the relationship between polymorphisms of rs1532624 and rs289741 loci in cholesteryl ester transfer protein(CETP) genes and atherosclerotic cerebral infarction(ACI). Methods: The CETP gene rs...Objective: To investigate the relationship between polymorphisms of rs1532624 and rs289741 loci in cholesteryl ester transfer protein(CETP) genes and atherosclerotic cerebral infarction(ACI). Methods: The CETP gene rs1532624 and rs289741 in 95 patients with ACI and 177 healthy subjects were genotyped by Mass ARRAY mass spectrometry. Each locus genotype and allele frequency distributions were compared. Results: The difference of allele frequency distribution between the rs1532624(χ~2=1.723, P=0.189) and rs289741(χ~2=2.466, P=0.116) were not statistically significant. The frequency distribution of rs1532624 genotype between the cerebral infarction group and healthy control group was statistically significant(χ~2=7.096, P=0.029), while rs289741 genotype frequency distribution between the two groups was not statistically significant(χ~2=2.906, P=0.234). Conclusion: ACI have a positive correlation with rs1532624 polymorphism, and AA genotype may be susceptible factors of ACI.展开更多
AIM: To determine the significance of cholesteryl ester transfer protein(CETP) in lipoprotein abnormalities in chronic hepatitis C virus(HCV) infection.METHODS: We evaluated the significance of the serum concentration...AIM: To determine the significance of cholesteryl ester transfer protein(CETP) in lipoprotein abnormalities in chronic hepatitis C virus(HCV) infection.METHODS: 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. RESULTS: 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/m L vs 2.40 ± 1.00 μg/m L, 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/m L vs 28.14 ± 9.94 μg/m L, P = 0.001) and high-density lipoprotein(HDL)(mean ± SD, 25.9 ± 7.34 μg/m L vs 17.17 ± 4.82 μg/m L, P < 0.001) were significantly higher in patientswith 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). CONCLUSION: Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.展开更多
Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that plays an important role in decreasing high-density lipoprotein cholesterol (HDL-C) levels and increasing low-density lipoprotein cholesterol ...Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that plays an important role in decreasing high-density lipoprotein cholesterol (HDL-C) levels and increasing low-density lipoprotein cholesterol (LDL-C) levels. Inhibition of CETP may be a new therapy for treating atherosclerosis. Herein, we report the development of a ligand-based pharmacophore model and pharmacophore-based virtual screening of the ZINC/big-n-greasy database, leading to the identification of compound H-10 as a potential CETP inhibitor in vitro. Based on H-10, a series of 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides were designed, synthesized, and evaluated against CETP. Compound 41 was found to have the best activity, resulting in 85.0% inhibition of CETP at l0 μmol/L.展开更多
Objective: To assess whether the TaqIB polymorphism of cholesteryl ester transfer protein (CETP) is associated with coronary artery disease (CAD) in Chinese population, we performed a meta-analysis in this paper. Meth...Objective: To assess whether the TaqIB polymorphism of cholesteryl ester transfer protein (CETP) is associated with coronary artery disease (CAD) in Chinese population, we performed a meta-analysis in this paper. Methods: We searched PubMed, Embase, the Science Citation Index (SCI), the China Biological Medicine database (CBM), the China National Knowledge Infrastructure (CNKI), and the Wanfang database for relevant articles. Data were extracted, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: The lit- erature search yielded 448 studies, in which 10 case-control studies including 1 694 cases and 1 456 controls matched the selection criteria. The combined B1 and B2 allele frequencies were 0.587 and 0.413, respectively. The pooled OR was 1.10 (95% CI, 0.89-1.34) for comparing the B1B1 or B1B2 carriers with B2B2 carriers, and was 1.27 (95% CI, 1.09-1.49) in the B1B1 carriers versus B2B2 or B1B2 carriers. Conclusions: In the present study, the TaqIB poly- morphism of CETP was found to be associated with CAD in the Chinese population.展开更多
Cholesteryl ester transfer protein (CETP), an important regulatory factor in reverse cholesterol transport, has been investigated in relation to plasma HDL cholesterol, which is associated with restenosis after perc...Cholesteryl ester transfer protein (CETP), an important regulatory factor in reverse cholesterol transport, has been investigated in relation to plasma HDL cholesterol, which is associated with restenosis after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation. We examined the effect of plasma CETP activity and the Taq1B polymorphism on restenosis in Chinese HaM population. Methods and Results Our study included 228 patients with symptomatic coronary artery disease (CAD). The genotype of the subjects for Taq1B polymorphism of CETP was analyzed by using polymerase chain reaction-restriction fragment length poly- morphism (PCR-RFLP). In-stent restenosis (ISR) was observed in 93 patients (40.8 %). Baseline clinical, angiographic,and procedural characteristics data were not significantly different in patients with and without restenosis,except previous history of myocardial infarction (MI), left ventricular ejection fraction (LVEF), statin medication, and stent type. Taq1B polymorphism and plasma activity of CETP were not associated with the incidence of ISR (P = 0.68, P = 0.30, respectively). Linear regression analysis revealed that the risk of ISR was statistically significant correlation with stent type, LVEF, statin medication, and lesion length (P 〈 0.05). Conclusions Useful markers for risk of ISR were stent type, LVEF, statin medication and lesion length but not the Taq1B polymorphism and plasma activity of CETP.展开更多
Several epidemiological studies have clearly shown that low plasma levels of high density lipoprotein cholesterol (HDL-C) represent a cardiovascular disease (CVD) risk factor. However, it is unclear if there is a caus...Several epidemiological studies have clearly shown that low plasma levels of high density lipoprotein cholesterol (HDL-C) represent a cardiovascular disease (CVD) risk factor. However, it is unclear if there is a causal association between HDL-C concentration and CVD. A recent study published in the Lancet, which performed two Mendelian randomization analyses, showed that increased HDL-C levels were not associated with a decreased risk of myocardial infarction. These findings, together with the termination of the niacin-based AIM-HIGH trial and the discontinuation of cholesteryl ester transfer protein inhibitor dalcetrapib, challenge the concept that raising of plasma HDL-C will uniformly translate into reductions in CVD risk. HDL particles exhibit several anti-atherosclerotic properties, such as anti-inflammatory and anti-oxidative activities and cellular cholesterol efflux activity. Furthermore, HDL particles are very heterogeneous in terms of size, structure, composition and metabolism. HDL functionality may be associated more strongly with CVD risk than the traditional HDL-C levels. More research is needed to assess the association of the structure of HDL particle with its functionality and metabolism.展开更多
目的探讨冠心病患者血清磷脂转运蛋白(phospholipid transfer protein,PLTP)、胆固醇酯转运蛋白(cholesteryl ester transfer protein,CETP)水平与中医病证的相关性,为冠心病证候客观化和开发临床治疗药物探索新的途径。方法选择经冠状...目的探讨冠心病患者血清磷脂转运蛋白(phospholipid transfer protein,PLTP)、胆固醇酯转运蛋白(cholesteryl ester transfer protein,CETP)水平与中医病证的相关性,为冠心病证候客观化和开发临床治疗药物探索新的途径。方法选择经冠状动脉造影确诊为冠心病的患者201例,采用国内外公认标准,构建证候四诊合参数据库,进行中医辨证。随机选取健康体检者20名为健康对照组。取静脉血分离血清,分别以酶联免疫法测定血清PLTP、CETP表达;采用乙酰丙酮显色法测定甘油三酯(triglyceride,TG)含量;采用沉淀漂浮酶联法测定总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)含量。结果各证型冠心病患者血清PLTP、CETP、TC明显高于健康对照组,差异有统计学意义(P<0.05,P<0.01);各证型组血清TG、HDL-C、LDL-C与健康对照组比较,差异有统计学意义(P<0.05,P<0.01)。标实证组各证型血清PLTP与本虚组各证型比较,差异有统计学意义(P<0.05)。标实证组各证型血清TG、HDL-C、LDL-C与本虚组各证型比较,差异有统计学意义(P<0.05、P<0.01)。结论标实证冠心病患者血清PLTP表达明显升高。标实证冠心病患者血清脂质改变较本虚证更为显著。展开更多
基金supported by grants from Natural Science Foundation of China(31501018,31760310,and 81660224)the Social Development Project of Hainan Province(SF201401)
文摘Objective: To investigate the relationship between polymorphisms of rs1532624 and rs289741 loci in cholesteryl ester transfer protein(CETP) genes and atherosclerotic cerebral infarction(ACI). Methods: The CETP gene rs1532624 and rs289741 in 95 patients with ACI and 177 healthy subjects were genotyped by Mass ARRAY mass spectrometry. Each locus genotype and allele frequency distributions were compared. Results: The difference of allele frequency distribution between the rs1532624(χ~2=1.723, P=0.189) and rs289741(χ~2=2.466, P=0.116) were not statistically significant. The frequency distribution of rs1532624 genotype between the cerebral infarction group and healthy control group was statistically significant(χ~2=7.096, P=0.029), while rs289741 genotype frequency distribution between the two groups was not statistically significant(χ~2=2.906, P=0.234). Conclusion: ACI have a positive correlation with rs1532624 polymorphism, and AA genotype may be susceptible factors of ACI.
文摘AIM: To determine the significance of cholesteryl ester transfer protein(CETP) in lipoprotein abnormalities in chronic hepatitis C virus(HCV) infection.METHODS: 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. RESULTS: 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/m L vs 2.40 ± 1.00 μg/m L, 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/m L vs 28.14 ± 9.94 μg/m L, P = 0.001) and high-density lipoprotein(HDL)(mean ± SD, 25.9 ± 7.34 μg/m L vs 17.17 ± 4.82 μg/m L, P < 0.001) were significantly higher in patientswith 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). CONCLUSION: Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.
文摘Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that plays an important role in decreasing high-density lipoprotein cholesterol (HDL-C) levels and increasing low-density lipoprotein cholesterol (LDL-C) levels. Inhibition of CETP may be a new therapy for treating atherosclerosis. Herein, we report the development of a ligand-based pharmacophore model and pharmacophore-based virtual screening of the ZINC/big-n-greasy database, leading to the identification of compound H-10 as a potential CETP inhibitor in vitro. Based on H-10, a series of 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino) propanamides were designed, synthesized, and evaluated against CETP. Compound 41 was found to have the best activity, resulting in 85.0% inhibition of CETP at l0 μmol/L.
基金Project supported by the National Natural Science Foundation of China(Nos. 30900526 and 81070250)the Fundamental Research Funds for the Central Universitiesthe China Postdoctoral Science Foundation(No. 20100471616)
文摘Objective: To assess whether the TaqIB polymorphism of cholesteryl ester transfer protein (CETP) is associated with coronary artery disease (CAD) in Chinese population, we performed a meta-analysis in this paper. Methods: We searched PubMed, Embase, the Science Citation Index (SCI), the China Biological Medicine database (CBM), the China National Knowledge Infrastructure (CNKI), and the Wanfang database for relevant articles. Data were extracted, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: The lit- erature search yielded 448 studies, in which 10 case-control studies including 1 694 cases and 1 456 controls matched the selection criteria. The combined B1 and B2 allele frequencies were 0.587 and 0.413, respectively. The pooled OR was 1.10 (95% CI, 0.89-1.34) for comparing the B1B1 or B1B2 carriers with B2B2 carriers, and was 1.27 (95% CI, 1.09-1.49) in the B1B1 carriers versus B2B2 or B1B2 carriers. Conclusions: In the present study, the TaqIB poly- morphism of CETP was found to be associated with CAD in the Chinese population.
基金Natural Science Foundation of Guangdong Province,China(No.5001160)
文摘Cholesteryl ester transfer protein (CETP), an important regulatory factor in reverse cholesterol transport, has been investigated in relation to plasma HDL cholesterol, which is associated with restenosis after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation. We examined the effect of plasma CETP activity and the Taq1B polymorphism on restenosis in Chinese HaM population. Methods and Results Our study included 228 patients with symptomatic coronary artery disease (CAD). The genotype of the subjects for Taq1B polymorphism of CETP was analyzed by using polymerase chain reaction-restriction fragment length poly- morphism (PCR-RFLP). In-stent restenosis (ISR) was observed in 93 patients (40.8 %). Baseline clinical, angiographic,and procedural characteristics data were not significantly different in patients with and without restenosis,except previous history of myocardial infarction (MI), left ventricular ejection fraction (LVEF), statin medication, and stent type. Taq1B polymorphism and plasma activity of CETP were not associated with the incidence of ISR (P = 0.68, P = 0.30, respectively). Linear regression analysis revealed that the risk of ISR was statistically significant correlation with stent type, LVEF, statin medication, and lesion length (P 〈 0.05). Conclusions Useful markers for risk of ISR were stent type, LVEF, statin medication and lesion length but not the Taq1B polymorphism and plasma activity of CETP.
文摘Several epidemiological studies have clearly shown that low plasma levels of high density lipoprotein cholesterol (HDL-C) represent a cardiovascular disease (CVD) risk factor. However, it is unclear if there is a causal association between HDL-C concentration and CVD. A recent study published in the Lancet, which performed two Mendelian randomization analyses, showed that increased HDL-C levels were not associated with a decreased risk of myocardial infarction. These findings, together with the termination of the niacin-based AIM-HIGH trial and the discontinuation of cholesteryl ester transfer protein inhibitor dalcetrapib, challenge the concept that raising of plasma HDL-C will uniformly translate into reductions in CVD risk. HDL particles exhibit several anti-atherosclerotic properties, such as anti-inflammatory and anti-oxidative activities and cellular cholesterol efflux activity. Furthermore, HDL particles are very heterogeneous in terms of size, structure, composition and metabolism. HDL functionality may be associated more strongly with CVD risk than the traditional HDL-C levels. More research is needed to assess the association of the structure of HDL particle with its functionality and metabolism.