Cholesteryl Ester Transfer Protein TaqIB Polymorphism Research Articles

The combined effects of cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism and canola, sesame and sesame-canola oils consumption on metabolic response in patients with diabetes and healthy people.

Introduction: Cholesteryl ester transfer protein (CETP) is a key regulating enzyme in the lipid metabolism pathway, and its gene polymorphism may be a candidate for modulating the metabolic responses to dietary intervention. We thus examined whether the effects of the CETP TaqIB polymorphism on metabolic profiles were modified by dietary plant oils. Methods: This is a retrospective analysis of data collected during a randomized triple-blind cross over trial. A total of 95 patients with type 2 diabetes and 73 non-diabetes individuals completed a 9-weekof the intake of sesame, canola and sesame-canola oils. Blood samples were collected at the beginning and at the end of each intervention period for biochemical analysis. Genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: In diabetes patients, B1B1 homozygotes of the CETP TaqIB polymorphism compared with B2 carriers (B1B2 + B2B2) had significantly lower diastolic blood pressure, apoB and apoB: apoA-1,and higher Lp(a) after the intake of sesame-canola oil, as well as lower insulin and HOMA-IR after the intake of sesame oil. There was also a significant effect of genotype on adjusted changes of apoB, apoB: apoA-1, insulin, HOMA-IR and QUICKI. A significant genotype-dietary oils combined effects were observed for diastolic blood pressure, and LDL: HDL, TC: HDL and TG: HDL ratios in diabetes patients. No independent or combined effects of dietary oils and genotypes on outcomes were found in healthy people. Conclusion: There was a modulatory effect of the CETP TaqIB polymorphism on some metabolic traits in response to plant oils in patients with diabetes. Taken together, the intake of sesame-canola and canola oils showed more favorable effects in diabetes patients with B1B1 genotype. Future investigations are needed to confirm these results.

Association of APOE and CETP TaqIB Polymorphisms with Type 2 Diabetes Mellitus

Apolipoprotein E (APOE) and cholesteryl ester transfer protein (CETP) play an important role in the lipid metabolism. Dyslipidemia is one of the complications that found in type 2 diabetes mellitus (T2DM) patients. The aim of this study was to investigate the association of APOE and CETP TaqIB polymorphisms with T2DM and its related metabolic parameters in Southern Thai population. Study subjects were 241 T2DM patients and 275 healthy controls. The APOE and CETP TaqIB polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. APOE polymorphism showed a statistical difference in allele frequencies (p=0.025) and genotype distributions (p<0.001) between T2DM patients and healthy controls. The E4 carriers were associated with a significantly higher TC, and/or LDL-C levels compared to the E2 and E3 carriers, respectively in all subjects and healthy controls. Moreover, CETP TaqIB B2B2 genotype was significantly higher HDL-C levels compared with B1B1, and B1B2 genotypes in all subjects, and T2DM patients. Multiple logistic regression analysis showed that APOE and CETP TaqIB polymorphisms were not associated with T2DM. In conclusion, APOE and CETP TaqIB polymorphisms might not be the genetic risk factors for T2DM in Southern Thai population, however, APOE and CETP TaqIB polymorphisms were associated with serum lipids in healthy controls and T2DM, respectively.

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.

The effect of APOE, CETP, and PCSK9 polymorphisms on simvastatin response in Thai hypercholesterolemic patients.

To investigate the effect of apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and proprotein convertase subtilisin kexin type 9 (PCSK9) polymorphisms on the lipid-lowering response to simvastatin therapy in Thai hypercholesterolemic patients. Two hundred and twenty-five hypercholesterolemic patients in southern Thailand were enrolled and treated with simvastatin 20 or 40mg per day for 3months. Serum lipids were measured before and after the therapy. APOE, CETP TaqIB, and PCSK9 (R46L, I474V, and E670G) polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). After 3months of simvastatin therapy, subjects with APOE2 (Total cholesterol [TC]: -30.89% vs-13.56%, P<.05, LDL-C: -45.00% vs -17.73%, P<.05) and APOE3 carriers (TC: -26.22% vs -13.56%, P<.05, LDL-C: -37.14% vs -17.73%, P<.05) had greater TC and LDL-C reduction compared to APOE4 carriers, whereas CETP TaqIB B2B2 genotype showed lower TC (-16.37% vs -24.92%, P=.016) and LDL-C (-22.54% vs -35.19%, P=.028) reduction compared to CETP TaqIB B1 carriers. In addition, PCSK9 474IV carriers showed greater LDL-C (-50.57% vs -32.99%) reduction compared to PCSK9 474II carriers. Combined effect analyses showed that individuals carrying more risk alleles tended to have lower TC and LDL-C (P for trend=.000 and .000, respectively) reduction in response to simvastatin therapy. APOE4 carriers and the CETP TaqIB B2B2 genotype were associated with a decreased response, but PCSK9 474IV carriers tended to be associated with an increased response to simvastatin therapy in Thai hypercholesterolemic patients.

Effect of Cholesteryl Ester Transfer Protein Gene TaqIB Polymorphism on the Risk of Ischemic Stroke: A Meta-Analysis

The association between cholesteryl ester transfer protein (CETP) TaqIB polymorphism and ischemic stroke (IS) risk has generated conflicting results. To investigate whether the TaqIB polymorphism of the CETP gene was associated with the risk of IS, a meta-analysis was performed. Studies were retrieved by searching PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Wanfang Database, and the Chinese VIP Database before January 16, 2017. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the association. Depending on the heterogeneity the fixed-effects model or the random-effects model was used. A total of 6 case-control studies were identified with 1494 cases and 1370 controls. Overall, an association of CETP TaqIB polymorphism with IS was found in the 4 genetic models (B2B2 versus B1B1: OR = .63, 95% CI = .51-.79, P < .001; B1B2 + B2B2 versus B1B1: OR = .75, 95% CI = .64-.87, P < .001; B2B2 versus B1B2 + B1B1: OR = .70, 95% CI = .57-.85, P < .001; B2 versus B1: OR = .78, 95% CI = .70-.87, P < .001). In the subgroup analysis by ethnicity, similar risks were also observed in Asian population. This meta-analysis indicates that CETP TaqIB polymorphism is associated with IS risk, and the B2 allele is a protective factor for IS.

Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis.

Background: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism (rs708272), the risk of developing composite ischemic cardiovascular disease (CVD) and the concentration of high-density lipoprotein cholesterol (HDL-C), but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. Methods: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. Results: Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09–1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. Results suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36–0.65, p < 0.001. Conclusions: The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians.

0106: Association of lipoproteina and cholesteryl ester transfer protein-TaqIB polymorphism in Tunisian type 2 diabetes

Lipoprotein (a) [Lp(a)] is a plasma lipoprotein consisting of a LDL-like particle with a molecule of apolipoprotein B100 covalently linked to a very large additional glycoprotein known as apolipoprotein(a). Elevated Lp(a) levels constitute an independent risk factor for cardiovascular disease in the general population. Several studies have examined the possibility that type 2 diabetes could influence Lp(a) concentrations. Cholesteryl ester transfer protein (CETP) plays a key role in lipoprotein metabolism, promoting the exchange of triglycerides (TGs) and cholesteryl esters (CEs) between lipoprotein particles. The CETP TaqIB polymorphism in type 2 diabetes may have an increased risk for coronary artery disease. The aim of the present study was to examine the effect of the genetic polymorphism TaqIB of the CETP on the Lp(a) concentrations and the risk of coronaropathy in a cohort of type 2 diabetes. Plasma Lp(a) levels are not significantly associated with CETP TaqIB polymorphism in type 2 diabetes: no significant difference in the plasma Lp (a) between the diabetics having the genotype B1B1 and those having the genotype B2 (365.8±259 vs. 317±250.1mg; p=0.20). For the diabetics with genotype B1B1, Lp (a) was correlated significantly with the LDL (n=90, r=0.32; p=0.002) and the apoB (n=90, r=0.24, p=0.01). The proportion of the diabetics having the allèle B2 and Lp (a) superior to 300mg/l, is clearly more important at those having coronaropathy (51.1 vs. 29.2%; odds ratio=2.53; p=0.03). Lp(a) levels is a risk factor for cardiovascular disease in type 2 diabetic patients. This atherogenic risk seems to depend on the genetic polymorphism TaqIB of the CETP.

Studies of the CETP TaqIB and ApoE Polymorphisms in Southern Thai Subjects with the Metabolic Syndrome.

Several genetic factors have been investigated responsible for metabolic syndrome (MetS). The aim of this study was to investigate the association between cholesteryl ester transfer protein (CETP) TaqIB and apolipoprotein E (ApoE) polymorphisms and MetS in 378 subjects from Southern Thailand. Subjects were divided into MetS+ (n = 121) and MetS- (n = 257) groups according to the criteria of National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII). The CETP TaqIB and ApoE polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Logistic regression analysis revealed no association of CETP TaqIB and ApoE variants with MetS, after adjustment for age and sex. However, ε4 allele had a significantly increased odds ratio (OR) of reduced high-density lipoprotein-cholesterol (HDL-C) levels when compared with ε3 allele (OR 1.91; 95% CI 1.11-3.29, p = 0.020). This suggests that CETP TaqIB and ApoE polymorphisms may not be considered as genetic risk factors for MetS in a Southern Thai population. However, ε4 allele which is associated with one metabolic component, low HDL-C levels, might predispose the subjects to develop metabolic disturbances.

Meta-analysis of cholesteryl ester transfer protein TaqIB polymorphism and risk of myocardial infarction.

A number of studies have been conducted to explore the association between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism and risk of myocardial infarction (MI); however, the results are inconsistent. Therefore, we conducted this meta-analysis to clarify the issue based on all the data available.Eligible studies were retrieved by searching PubMed, Embase, Web of Science, and Google Scholar. We calculated the crude odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) to assess the association between the TaqIB polymorphism and risk of MI.We included 13 studies involving 8733 MI cases and 8573 controls in the meta-analysis. The pooled results from all included studies showed decreased MI risk in the analysis of the B2B2 versus B1B1 (OR = 0.78, 95% CI = 0.68-0.91), dominant (OR = 0.88, 95% CI = 0.77-0.99), and recessive genetic models (OR = 0.84, 95% CI = 0.78-0.91). The frequency of the B2B2 genotype in MI patients was lower (OR = 0.87, 95% CI = 0.81-0.94). However, there was no significant association in the B1B2 versus B1B1 analysis (OR = 0.92, 95% CI = 0.81-1.05) and no significant difference for the B1B1 genotype (OR = 1.04, 95% CI = 0.98-1.11) and B1B2 genotype (OR = 1.03, 95% CI = 0.97-1.08). Cumulative analysis confirmed these results.Our results suggest that the B2B2 genotype of the CETP TaqIB polymorphism is a protective factor against the development of MI.

CETP TaqIB genotype modifies the association between alcohol and coronary heart disease: The INTERGENE case-control study

Alcohol consumption at moderate levels has been associated with decreased risk of coronary heart disease (CHD). However, the cardio-protective effect of alcohol may be restricted to subjects with a particular genotype of the cholesteryl ester transfer protein (CETP) polymorphism. There is evidence for this from one study in men, but the finding has not been confirmed since. The present study specifically re-examines the potential modification of the association between alcohol consumption and CHD by the CETP TaqIB (rs708272) polymorphism in a sample including both men and women. The INTERGENE case-control study consists of 618 patients with CHD and 2921 control subjects, of whom 19% were homozygous for the CETP TaqIB B2 allele. Alcohol consumption was categorized into sex-specific tertiles of ethanol intake, with non-drinkers constituting a separate category. Logistic regression was used to determine the association between CHD with genotype, ethanol intake, and their interaction. Participants with intermediate ethanol intake (2nd tertile) had lower risk of CHD than those with low ethanol intake (odds ratio [OR] = 0.65; 95% confidence interval [CI] 0.50–0.85). The strongest protective association was seen in the CETP TaqIB B2 homozygotes for intermediate vs. low ethanol intake (odds ratio OR = 0.21; 95% CI 0.10–0.44). The interaction between ethanol intake and genotype was statistically significant (p = 0.008), and of similar size in men and women though significant only in men (p = 0.01). The effect modification could not be explained by differences in lifestyle, socioeconomics, or alcohol-related biological variables such as HDL–cholesterol. Our study is the first to replicate previous findings of an effect modification in men. It gives only suggestive results for women, possibly due to the small number of female cases (n = 165). The prevented fraction for the favorable combination of genotype and alcohol consumption is about 6%, a value suggesting that the cardio-protective effect of moderate alcohol consumption applies only to a small segment of the general population.

Cholesteryl ester transfer protein TaqIB polymorphism and its association with serum lipid levels and longevity in Chinese Bama Zhuang population.

BackgroundTaqIB polymorphism in the cholesteryl ester transfer protein (CETP) gene has been reported to be associated with serum high-density lipoprotein cholesterol (HDL-C) levels and longevity in several populations, but controversial results also arose probably due to racial/ethnic diversity. Bama is a remote and mountainous county located in the northwest of Guangxi, People's Republic of China, which has been well known for its longevity for centuries. The current study was to investigate the possible association of CETP TaqIB polymorphism with serum lipid levels and longevity in the Bama Zhuang population.MethodsThe CETP TaqIB genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism in 523 long-lived inhabitants (long-lived group, LG; aged 90-107 years) and 498 healthy controls without longevity family history (non-long-lived group, non-LG; aged 40-69 years) residing in Bama County.ResultsThe levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were higher but TG, HDL-C/LDL-C ratio and the prevalence of dyslipidemia were lower in LG than in non-LG (P < 0.001 for all). There were no differences in the allelic and genotypic frequencies between the two groups (P > 0.05). Serum HDL-C levels and HDL-C/LDL-C ratio in LG were different among the genotypes (P < 0.01 for each), the subjects with B2B2 and B1B2 genotyes had higher HDL-C levels and HDL-C/LDL-C ratio than the subjects with B1B1genotye, whereas the levels of TC and HDL-C in non-LG were different among/between the genotypes (P < 0.01 for each), the B2 allele carriers had lower TC and higher HDL-C levels than the B2 allele noncarriers. Serum TG and HDL-C levels and HDL-C/LDL-C ratio were correlated with genotypes in LG, whereas serum TC and HDL-C levels were associated with genotypes in non-LG (P < 0.05-0.001).ConclusionsThe association of CETP TaqIB polymorphism and serum lipid profiles is different between LG and non-LG in the Chinese Bama Zhuang population. CETP TaqIB polymorphism might be one of the longevity-related genetic factors in this population.

Effect of Genetic Variants Related to Lipid Metabolism as Risk Factors for Cholelithiasis After Bariatric Surgery in Brazilian Population

The manifestation of cholelithiasis after bariatric surgery may depend on genetic factors related to lipid metabolism, including apolipoprotein E (APOE) and cholesteryl ester transfer protein (CETP) gene polymorphisms. We investigated the association between APOE HhaI and CETP TaqIB polymorphisms [PCR-RFLP] and occurrence of cholelithiasis over up to 8months of follow-up after gastroplasty to Roux-en-Y gastric bypass in 220 patients distributed in Group 1 (G1) 114 with cholelithiasis postoperatively and Group 2 (G2) 106 without cholelithiasis, including biochemical and anthropometric profiles analyses. In our series, the allelic and genotypic distributions of CETP TaqIB and APOE HhaI polymorphisms were similar in both groups (P > 0.05). The subgroup analysis evidenced that 54% of the patients from G1, APOE*4 allele carriers compared with APOE*3/3 carriers, presented altered low-density lipoprotein cholesterol (LDL cholesterol) serum levels (P = 0.022) before bariatric surgery. The B1 allele for CETP was associated to more quickly elevation of HDL cholesterol levels just in individuals without cholelitiasis (P < 0.0001). The multivariate logistic regression analysis demonstrates correlation between APOE*4 allele, higher total cholesterol (TC) serum levels and prediposition to cholelitiasis in preoperative period. However, the presence of postoperative cholelithiasis was not associated with altered lipid profile. The CETP TaqIB and APOE HhaI polymorphisms do not seem to have association with gallstones in the late postoperative bariatric surgery, considering that these genetic variants do not differ subgroups of patients who are eligible to routine prophylactic cholecystectomy, at least in Brazilian population.

Diff erential eff ect of ATP binding cassette transporter A1 R219K and cholesteryl ester transfer protein TaqIB genotypes on HDL-C levels in overweight/obese and non-obese Chinese subjects

Objectives ATP-binding cassette transporter A1 (ABCA1) and cholesteryl ester transfer protein (CETP) are involved in the HDL metabolism and play a key role in reverse cholesterol transport. The study aim was mainly to examine the possible association of the ABCA1 and CETP polymorphisms with overweight/obesity in a South-West Chinese population.Methods and results Three hundred and thirty-eight Han Chinese (206 overweight/obese and 132 normal control subjects) in Chengdu area were studied using the PCR-RFLP analysis. The genotype and allele frequencies of the ABCA1 R219K, CETP Taq IB and -629C > A polymorphisms in cases of overweight/obesity showed no signifi cant statistical diff erence compared to those of the control subjects. However, on analysis of the HDL-C levels, cases showed statistically higher levels among those carrying the ABCA1 KK genotype compared to RR genotype carriers, and controls having the CETP B2B2 genotype had a marginally signifi cantly higher serum HDL-C concentration than those of the B1B1 genotype. In addition, the combined genotype eff ect of the ABCA1 R219K and the CETP Taq IB polymorphisms on HDL-C levels was evident in the control subjects: the carriers of the KK/B2B2 genotype showed the highest levels of HDL-C (2.23 ± 0.91 mmol/L), whereas those of the RR/B1B1 genotype showed the lowest (1.32 ± 0.33 mmol/L). There were signifi cant diff erences of the HDL-C levels between subjects with genotype KK/B2B2 and those with each of the other genotype combinations (all P < 0.05).Conclusion Polymorphisms of the ABCA1 and CETPgenes are associated with altered plasma HDL-C concentrations. These associations on HDL-C levels are modifi ed by BMI in a Chinese population of the Chengdu area.

Cholesteryl Ester Transfer Protein Gene and Effectiveness of Lipid Lowering of Atorvastatin

Cholesteryl ester transfer protein (CETP) plays a key role in lipid metabolism. Thus, variations in the CETP gene may be clinically relevant. Newly started atorvastatin users (n=212) were genotyped for CETP genetic variants (TaqIB and I405V). Homozygotes for B1 allele of TaqIB polymorphism had lower plasma high density lipoprotein cholesterol (HDL-C) compared with B1B2 or B2B2 genotypes (p=0.03, for each). Homozygotes for I allele of I405V polymorphism had lower plasma HDL-C compared with IV or VV genotypes (p=0.001, for each). In the whole population, the B1 carriers increased HDL-C levels by 4% after atorvastatin treatment, compared with B2 carriers, where a 4% decrease occurred (p=0.03). Also homozygotes for B1 allele decreased triglyceride levels to a lesser, though not significant, degree compared to B1B2 or B2B2 genotypes. CETP TaqIB or I405V polymorphisms seem to modify the lipid lowering response to atorvastatin treatment. This knowledge may help design more effective hypolipidaemic treatment.

Response to Letter Regarding Article, “Association of Circulating Cholesteryl Ester Transfer Protein Activity With Incidence of Cardiovascular Disease in the Community”

HomeCirculationVol. 122, No. 6Response to Letter Regarding Article, “Association of Circulating Cholesteryl Ester Transfer Protein Activity With Incidence of Cardiovascular Disease in the Community” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Letter Regarding Article, “Association of Circulating Cholesteryl Ester Transfer Protein Activity With Incidence of Cardiovascular Disease in the Community” Ramachandran S. Vasan, MD, Michael J. Pencina, PhD, Sander J. Robins, MD and Ralph B. D'Agostino, PhD Guneet Kaur, PhD Justin P. Zachariah, MD Jose M. Ordovas, PhD Ramachandran S. VasanRamachandran S. Vasan Framingham Heart Study, Framingham, Mass Search for more papers by this author , Michael J. PencinaMichael J. Pencina Framingham Heart Study, Framingham, Mass Search for more papers by this author , Sander J. RobinsSander J. Robins Framingham Heart Study, Framingham, Mass Search for more papers by this author and Ralph B. D'AgostinoRalph B. D'Agostino Framingham Heart Study, Framingham, Mass Search for more papers by this author Guneet KaurGuneet Kaur Department of Mathematics and Statistics, Boston University, Boston, Mass Search for more papers by this author Justin P. ZachariahJustin P. Zachariah Department of Cardiology, Children’s Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, Mass Search for more papers by this author Jose M. OrdovasJose M. Ordovas Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Mass Search for more papers by this author Originally published10 Aug 2010https://doi.org/10.1161/CIRCULATIONAHA.110.951822Circulation. 2010;122:e421We thank Dr Quintão for correctly noting that the recent prospective analysis from our group using Framingham Offspring Study data indicated an inverse association of plasma cholesteryl ester transfer protein activity with the incidence of cardiovascular disease events,1 whereas a prior publication noted a direct relation of plasma cholesteryl ester transfer protein activity with the prevalence of coronary heart disease.2 We submit that differences in study design (prospective versus cross-sectional) likely account for these differences. We also submit that the risk of cardiovascular disease associated with any potential biomarker is best evaluated by longitudinal studies. Indeed, a recent study reported a similar inverse relation of plasma cholesteryl ester transfer protein concentration and cardiovascular mortality in a high-risk sample.3DisclosuresNone. References 1 Vasan RS, Pencina MJ, Robins SJ, Zachariah JP, Kaur G, D'Agostino RB, Ordovas JM. Association of circulating cholesteryl ester transfer protein activity with incidence of cardiovascular disease in the community. Circulation. 2009; 120: 2414–2420.LinkGoogle Scholar2 Ordovas JM, Cupples LA, Corella D, Otvos JD, Osgood D, Martinez A, Lahoz C, Coltell O, Wilson PW, Schaefer EJ. Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study. Arterioscler Thromb Vasc Biol. 2000; 20: 1323–1329.CrossrefMedlineGoogle Scholar3 Ritsch A, Scharnagl H, Eller P, Tancevski I, Duwensee K, Demetz E, Sandhofer A, Boehm BO, Winkelmann BR, Patsch JR, März W. Cholesteryl ester transfer protein and mortality in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health study. Circulation. 2010; 121: 366–374.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails August 10, 2010Vol 122, Issue 6 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.110.951822 Originally publishedAugust 10, 2010 PDF download Advertisement SubjectsEpidemiologyMetabolism

Genetic determinants of plasma HDL-cholesterol levels in prepubertal children

Introduction Genetic determinants have been related to variation of high-density lipoprotein cholesterol (HDL-C) levels, but the extension of this association remains controversial. In our study, we analyzed the contribution of several polymorphisms on HDL-C-related genes to variation of plasma HDL-C in prepubertal children. Methods We studied 1269 (641 males and 628 females) 6–8 years old healthy children, who participated in a cross-sectional study examining cardiovascular risk factors in Spain. Common genetic variants in the apolipoprotein AI, apolipoprotein AII, cholesteryl ester transfer protein (CETP), hepatic lipase, ATP-binding cassette transporter A1, and paraoxonase genes were determined by PCR. Results CETP TaqI B2 carrier girls had significantly higher HDL-C levels than B1B1 girls. B2B2 boys had significantly higher ( p < 0.001) HDL-C than B1B1and B1B2 boys. In linear regression analysis, CETP TaqIB appears as the main predictor of HDL-C plasma levels, accounting for 4.5% and 1.8% of HDL-C variation in girls and boys respectively. Conclusions Our data showed that among the studied polymorphisms only the CETP TaqIB polymorphism contributes to the variation in HDL-C levels in prepubertal children, particularly in girls, but overall these polymorphisms explain a small part of the variation of HDL-C plasma levels at this age.

Cholesteryl Ester Transfer Protein B1B1 Genotype Is Associated with a Parental History of Cardiovascular Diseases in Taiwanese People

Objective: To investigate the association between family history of cardiovascular disease (CVD) and cholesteryl ester transfer protein (CETP) TaqIB polymorphism in Taiwanese subjects. Subjects and Methods: In this cross-sectional study, 240 subjects (115 men and 125 women) were divided into two groups based on whether or not they had a parental history of CVD. Polymerase chain reaction/restriction fragment length polymorphism was used to analyze the genotype of the subjects for the TaqIB polymorphism of CETP in intron 1. Results: The frequency of the B1B1 genotype was significantly higher in Taiwanese subjects with a family history of CVD than in those without it (31.2 vs. 18.8%, odds ratio = 1.97, 95% confidence interval = 1.084–3.579, p = 0.035). Siblings with the B1B1 genotype had lower levels of serum high-density lipoprotein cholesterol (HDL-C) than siblings with either B1B2 (46.7 ± 11.0 vs. 52.5 ± 11.1 mg/dl, p = 0.034) or B2B2 genotypes (46.7 ± 11.0 vs. 55.2 ± 9.6 mg/dl, p = 0.01). Conclusion: CETP TaqIB polymorphism is associated with plasma HDL-C levels. The CETP B1B1 genotype may influence the susceptibility to CVD in Taiwan.

The association between high-density lipoprotein cholesterol level and cholesteryl ester transfer protein TaqIB gene polymorphism is influenced by alcohol drinking in a population-based sample

Cholesteryl ester transfer protein (CETP) is a key enzyme in high-density lipoprotein (HDL) cholesterol metabolism. We studied the association between CETP TaqIB polymorphism and the HDL cholesterol levels considering environmental factors in a population-based sample consisting of 1729 participants who did not use lipid-lowering agents (659 men and 1070 women). The CETP TaqIB genotypes were determined by PCR-RFLP analysis. The serum HDL cholesterol levels of female participants with the B2B2 genotype were significantly higher than those with other genotypes ( p < 0.001). Multiple regression analysis with covariates such as age, waist to hip (W/H) ratio, alcohol drinking, current smoking, non-HDL cholesterol, and logarithm of triglyceride revealed that the CETP TaqIB genotype was an independent determinant of HDL cholesterol levels in men ( p = 0.049) and women ( p < 0.001). Subgroup analysis revealed that an interaction was observed between the CETP TaqIB polymorphism and alcohol consumption in the regulation of HDL cholesterol levels in men ( p = 0.049) and women ( p = 0.022). No interactions were observed between the CETP TaqIB polymorphism and current smoking status, body mass index, or W/H ratio in the regulation of HDL cholesterol levels. The association between the CETP TaqIB polymorphism and HDL cholesterol levels was more evident in alcohol consumers than in non-drinkers.

The Effect of Cholesteryl Ester Transfer Protein −629C→A Promoter Polymorphism on High-Density Lipoprotein Cholesterol Is Dependent on Serum Triglycerides

The -629C-->A cholesteryl ester transfer protein (CETP) promoter polymorphism is a determinant of HDL cholesterol (HDL-C). The effect of the closely linked CETP TaqIB polymorphism on HDL-C has been suggested to be modified by obesity and hyperinsulinemia. Because the CETP-mediated cholesteryl ester transfer out of HDL is stimulated by high triglycerides, we hypothesized that triglycerides modify the effect of the CETP -629C-->A promoter polymorphism on HDL-C. In 7083 nondiabetic subjects of the PREVEND population, the -629C-->A promoter polymorphism, HDL-C, serum triglycerides, waist circumference, and insulin resistance (HOMA(ir)) were determined. Serum apolipoprotein A-I was available in 6948 subjects. The TaqIB polymorphism was also assessed. The study is set in the general community. HDL-C and serum apolipoprotein A-I were on average 0.14 mmol/liter and 0.05 g/liter higher in -629AA (22.9%) compared to -629CC (26.8%) homozygotes (P < 0.001 for both). This genotype effect on HDL-C was on average 0.15 mmol/liter in the lowest triglyceride tertile but only 0.08 mmol/liter in the highest tertile (P < 0.01). Multiple regression analysis showed that HDL-C was determined by the CETP promoter variant (P < 0.001), gender (P < 0.001), triglycerides (P < 0.001), and interactions between triglycerides and genotype (P < 0.05), between triglycerides and gender (P < 0.05), and between genotype and gender (P < 0.05), independently from waist, HOMA(ir), alcohol use, age, and use of lipid-lowering drugs. The TaqIB polymorphism also interacted with triglycerides on HDL-C. The -629C-->A promoter polymorphism did not interact with obesity and HOMA(ir) on HDL-C. The HDL-C-raising effect of the CETP -629A allele is diminished with higher triglycerides, which may be explained by a predominant effect of triglyceride-rich lipoproteins over circulating CETP itself on cholesteryl ester transfer out of HDL with rising triglycerides.

The cholesteryl ester transfer protein (CETP) TaqIB polymorphism in the cholesterol and recurrent events study: no interaction with the response to pravastatin therapy and no effects on cardiovascular outcome

Abstract Objectives On the basis of quantitative coronary angiography data, the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism has been postulated to predict the progression of coronary atherosclerosis and response to cholesterol-lowering therapy. Background Cholesteryl ester transfer protein mediates the exchange of lipids between anti-atherogenic high-density lipoprotein (HDL) and atherogenic apolipoprotein B containing lipoproteins and therefore plays a key role in human lipid metabolism. Hence, CETP gene polymorphisms may alter susceptibility to atherosclerosis. Methods To investigate the significance of the CETP TaqIB gene polymorphism with respect to clinical end points, we used the Cholesterol And Recurrent Events (CARE) cohort. The CARE study was designed to investigate the effect of five years of pravastatin therapy on coronary events. Results We found that the odds ratios for the primary end point were not significantly different from unity for the three genetic subgroups after five years of placebo treatment. Furthermore, pravastatin induced similar changes in total cholesterol, low-density lipoprotein cholesterol, and HDL cholesterol among TaqIB genotypes, and both nonfatal myocardial infarction and deaths from coronary heart disease were reduced to the same extent in all three genotypes. Conclusions In the CARE cohort, the CETP TaqIB polymorphism does not predict cardiovascular events or discriminate between those who will or will not benefit from pravastatin treatment.