1.Association of CETP gene I405V/D442G polymorphisms with cerebral hemorrhage and serum lipid profile in ethnic Han population from Changsha.
Xiaoyu XU ; Xiaoyu ZHENG ; Fuping JIE ; Yi ZENG ; Le ZHANG
Chinese Journal of Medical Genetics 2016;33(1):91-96
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
2.Influence of CETP gene -629C/A polymorphism on the efficacy of atorvastatin treatment and clinical outcome.
Jing GAO ; Hong-liang CONG ; Yong-min MAO ; Yi LIU ; Nan ZHANG ; Qian CHEN ; Ting LIU ; Rangzhuang CUI
Chinese Journal of Medical Genetics 2013;30(5):553-558
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
3.Study on the correlation between Chinese medical syndrome types and serum levels of PLTP and CETP in coronary heart disease patients.
Ping-ting ZHU ; Ping BO ; Yun SUN
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(6):749-752
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
4.Myocardial infarction patients show altered lipoprotein properties and functions when compared with stable angina pectoris patients.
Kyung Hyun CHO ; Dong Gu SHIN ; Suk Hwan BAEK ; Jae Ryong KIM
Experimental & Molecular Medicine 2009;41(2):67-76
Several parameters and risk factors were compared between Korean male myocardial infarction (MI) patients (n = 10) and angina pectoris (AP) patients (n = 17) to search unique biomarkers for myocardial infarction (MI) in lipoprotein level. Individual serum and lipoprotein fractions (VLDL, LDL, HDL2, HDL3) were isolated and analyzed by lipid and protein determination and enzyme assay. The MI group was found to have a 25 and 30% higher serum cholesterol and triacylglycerol (TG) level than the AP group, respectively, however, their body mass index (BMI), LDL-cholesterol (C), HDL-C, and glucose levels fell within the normal range. MI patients were found to have an approximately two-fold higher level of serum IL-6 and an 18% lower serum apoA-I level than that of the AP group. LDL and HDL2 fraction of the MI group were more enriched with TG than those of AP group. The increased TG was correlated well with the increased level of apoC-III in the same fraction. Cholesteryl ester transfer protein (CETP) activity and protein level were greatly increased in MI patients in the LDL and HDL3 fractions. MI patients showed more severely oxidized LDL fraction than patients in the AP group, as well as the weakest antioxidant ability of serum. Conclusively, MI patients were found to have unique serum and lipoprotein characteristics including increased IL-6 and TG in serum, with CETP and apoC-III in the LDL and HDL fractions, as well as severely impaired antioxidant ability of HDL.
Aged
;
Angina Pectoris/*blood
;
Apolipoprotein C-III/blood
;
Cholesterol Ester Transfer Proteins/blood
;
Copper/metabolism
;
Humans
;
Lipids/blood
;
Lipoproteins/*blood
;
Lipoproteins, LDL/blood
;
Male
;
Middle Aged
;
Myocardial Infarction/*blood
;
Oxidation-Reduction
;
Triglycerides/blood
5.Myocardial infarction patients show altered lipoprotein properties and functions when compared with stable angina pectoris patients.
Kyung Hyun CHO ; Dong Gu SHIN ; Suk Hwan BAEK ; Jae Ryong KIM
Experimental & Molecular Medicine 2009;41(2):67-76
Several parameters and risk factors were compared between Korean male myocardial infarction (MI) patients (n = 10) and angina pectoris (AP) patients (n = 17) to search unique biomarkers for myocardial infarction (MI) in lipoprotein level. Individual serum and lipoprotein fractions (VLDL, LDL, HDL2, HDL3) were isolated and analyzed by lipid and protein determination and enzyme assay. The MI group was found to have a 25 and 30% higher serum cholesterol and triacylglycerol (TG) level than the AP group, respectively, however, their body mass index (BMI), LDL-cholesterol (C), HDL-C, and glucose levels fell within the normal range. MI patients were found to have an approximately two-fold higher level of serum IL-6 and an 18% lower serum apoA-I level than that of the AP group. LDL and HDL2 fraction of the MI group were more enriched with TG than those of AP group. The increased TG was correlated well with the increased level of apoC-III in the same fraction. Cholesteryl ester transfer protein (CETP) activity and protein level were greatly increased in MI patients in the LDL and HDL3 fractions. MI patients showed more severely oxidized LDL fraction than patients in the AP group, as well as the weakest antioxidant ability of serum. Conclusively, MI patients were found to have unique serum and lipoprotein characteristics including increased IL-6 and TG in serum, with CETP and apoC-III in the LDL and HDL fractions, as well as severely impaired antioxidant ability of HDL.
Aged
;
Angina Pectoris/*blood
;
Apolipoprotein C-III/blood
;
Cholesterol Ester Transfer Proteins/blood
;
Copper/metabolism
;
Humans
;
Lipids/blood
;
Lipoproteins/*blood
;
Lipoproteins, LDL/blood
;
Male
;
Middle Aged
;
Myocardial Infarction/*blood
;
Oxidation-Reduction
;
Triglycerides/blood
6.Absence of association of the L296Q polymorphism in the cholesteryl ester transfer protein gene with type 2 diabetes mellitus in Chinese.
Yun GAO ; Lin ZHU ; Yang LONG ; Yan REN ; Tao CHEN ; Xiangxun ZHANG ; Haoming TIAN
Chinese Journal of Medical Genetics 2008;25(5):555-559
OBJECTIVETo investigate the association between L296Q polymorphism in the cholesterol ester transfer protein(CETP)gene and type 2 diabetes mellitus(T2DM)and blood lipids.
METHODSPlasma glucose and lipid levels were measured in a total of 303 subjects recruited from the West China Hospital of Sichuan University. The subjects were divided into 4 groups according to the levels of plasma glucose and triglyceride, namely T2DM with hypertriglyceridemia group, group of T2DM with normal triglyceride, group of hypertriglyceridemia without DM and group of normal controls, respectively. Genotypes of L296Q polymorphism in the CETP gene of all subjects were analyzed by real-time fluorescent quantitative PCR(FQ-PCR).
RESULTSNo significant differences were observed in the frequencies of genotypes LL and LQ and the 296Q allele among the four groups (chi-square=3.459, P>0.05; chi-square=3.155, P>0.05, respectively), nor the frequencies of genotypes LL and LQ between the T2DM and non-T2DM, or plasma lipid levels between the 296Q allele carriers and those of genotype LL.
CONCLUSIONNo association was found between the L296Q polymorphism in the CETP gene and T2DM as well as plasma lipid levels in various groups of Chinese in this study.
Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Cholesterol Ester Transfer Proteins ; genetics ; Diabetes Mellitus, Type 2 ; blood ; genetics ; pathology ; Female ; Gene Frequency ; Genotype ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA
7.Analysis of cholesterol ester transfer protein gene Taq IB and -629 C/A polymorphisms in patients with endogenous hypertriglyceridemia in Chinese population.
Yin WU ; Huai BAI ; Rui LIU ; Yu LIU ; Bing-wen LIU
Chinese Journal of Medical Genetics 2006;23(6):640-646
OBJECTIVETo investigate the variations of cholesterol ester transfer protein (CETP) gene and its relation to endogenous hypertriglyceridemia (HTG) in Chinese population.
METHODSOne hundred and thirty-five endogenous hypertriglyceridemics and 214 healthy subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphism (RFLPs) amplified by polymerase chain reaction (PCR). The polymorphic sites studied included Taq IB and -629 C/A polymorphism in CETP gene.
RESULTSThe frequencies of B(2) allele at Taq IB site in normal group and HTG group were 0.418 and 0.382, respectively. The frequencies of A allele at -629 C/A site in the two groups were 0.479 and 0.489, respectively. No significant difference between normal control and HTG groups were found in both allele frequency of the two polymorphism. Linkage disequilibrium was observed between Taq IB and -629 C/A polymorphic sites (D'=0.881). In the normal control group, subjects with genotype B(2)B(2) of Taq IB site had a higher serum mean concentration of HDL-C and lower LDL-C when compared with that of genotype B(1)B(1) and B(1)B(2), respectively (both P< 0.05), while those with genotype CC of -629 C/A site had a lower LDL-C level and higher Apo A II level when compared with that of genotype AC (P< 0.01 and P< 0.05, respectively). The changes of the lipid and lipoprotein levels were only observed in normal male subjects when male and female groups were further separated. No significant changes of lipid and lipoprotein levels were observed in both polymorphism in HTG group. Combined genotype analysis of the two sites, subjects with genotype B(2)B(2)CC in normal controls had higher HDL-C levels but lower serum triglyceride (TG) when compared with B(1)B(1)CC.
CONCLUSIONThese results suggest that Taq IB and -629 C/A polymorphisms in CETP gene are associated with healthy control subjects to some extent in Chinese population, but not with endogenous hypertriglyleridemia in the population group.
Adult ; Aged ; Aged, 80 and over ; Apolipoproteins ; blood ; Asian Continental Ancestry Group ; genetics ; China ; Cholesterol Ester Transfer Proteins ; genetics ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; DNA ; genetics ; metabolism ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertriglyceridemia ; blood ; ethnology ; genetics ; Linkage Disequilibrium ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Triglycerides ; blood
8.Effects of cholesterol ester transfer protein Taq1B polymorphism on response of serum HDL-C to dietary factors in hyperlipidemia patients.
Zhen-hui XU ; Hong-wei GUO ; Zhu-ying HUANG
Chinese Journal of Preventive Medicine 2006;40(4):269-272
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
9.Association between cholesteryl ester transfer protein gene polymorphisms and variations in lipid levels in patients with coronary heart disease.
Ke-qin ZHENG ; Si-zhong ZHANG ; Yong HE ; Li ZHANG ; Ke-lan ZHANG ; De-jia HUANG ; Yan SUN
Chinese Medical Journal 2004;117(9):1288-1292
BACKGROUNDThe Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD).
METHODSGenomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package.
RESULTSThe distribution of allele and genotype frequencies of the Taq/B, MspI, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq/B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047).
CONCLUSIONSGenetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq/B polymorphism is probably a genetic risk factor for CHD in the study population.
Adult ; Aged ; Carrier Proteins ; genetics ; Cholesterol Ester Transfer Proteins ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Disease ; blood ; genetics ; Female ; Gene Frequency ; Glycoproteins ; genetics ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Polymorphism, Genetic
10.Study on the association of cholesteryl ester transfer protein gene mutations with the susceptibility to coronary atherosclerotic heart disease.
Ke-qin ZHENG ; Si-zhong ZHANG ; Ke-lan ZHANG ; Li ZHANG ; Yong HE ; Xiang-dong KONG ; Yan SUN ; Zhi-guang SU
Chinese Journal of Medical Genetics 2003;20(1):23-26
OBJECTIVETo determine the frequencies of 4 mutations of cholesteryl ester transfer protein (CETP) gene in Chinese population and to investigate the association of the mutations with lipid metabolism and the susceptibility to coronary atherosclerotic heart disease (CHD).
METHODSThe target fragments of CETP gene were amplified and analyzed by PCR-restriction fragment length polymorphism technique in 209 unrelated control individuals and 203 CHD patients. The test for Hardy-Weinberg equilibrium was performed using HWE program and statistical analysis was implemented in statistical package SPSS.
RESULTSIVS14A and 451Q mutant genes were not found in either control group or patient group. The frequencies of 405V mutant allele were 0.443 and 0.413 in controls and patients, respectively, while 442G mutant gene frequencies were 0.007 and 0.025, respectively. The observed allele frequencies of I405V and D442G mutation were in accord with Hardy-Weinberg equilibrium. The frequency of 442G mutant gene in patients was significantly higher than that in controls (P=0.043). Compared with the CHD patients without D442G mutation, the 442G heterozygous CHD patients exhibited a significant increase in plasma TC and LDL-C concentration (P=0.017; P=0.041).
CONCLUSIONIVS14A and 451Q mutants of CETP gene were rare in Chinese population and 442G mutant gene was possibly one of the susceptibility factors to CHD in Chinese.
Aged ; Carrier Proteins ; genetics ; metabolism ; China ; Cholesterol Ester Transfer Proteins ; Coronary Artery Disease ; blood ; genetics ; DNA ; genetics ; metabolism ; DNA Restriction Enzymes ; metabolism ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Glycoproteins ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Mutation ; Polymorphism, Restriction Fragment Length

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