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Interaction of cholesterol ester transfer protein polymorphisms, body mass index, and birth weight with the risk of dyslipidemia in children and adolescents: the CASPIAN-III study.

ABSTRACT: OBJECTIVES:This study aims to investigate joint association between cholesterol ester transfer protein (CETP) polymorphisms and body mass index (BMI) or birth weight with the risk of dyslipidemia in Iranian children and adolescents. MATERIALS AND METHODS:This study was conducted as a sub-study of the "school-based nationwide health survey" (CASPIAN-III). We randomly selected 750 samples from the whole blood samples. Real-time PCR and high resolution melt (HRM) analysis were performed to determine Taq1B (rs708272) and A373P (rs5880) polymorphisms. RESULTS:Taq1B polymorphism increased HDL-C, and total cholesterol (TC) as well as decreased triglyceride and LDL-C concentrations. LDL-C and triglyceride levels were significantly higher and HDL-C and TC levels were significantly lower among those with A373P polymorphism. CT/TT genotype in Taq1B polymorphism showed a protective effect on dyslipidemia (OR= 0.12, 95% CI: 0.07-0.20). G allele of A373P polymorphism increased the risk of dyslipidemia (OR=4.10, 95% CI: 2.14, 7.83) after adjusting the confounders. We observed interactive effects of CETP gene polymorphisms and BMI or birth weight on dyslipidemia. CONCLUSION:Findings showed Taq1B polymorphism might have a protective effect and A373P polymorphism had deleterious effect on dyslipidemia in Iranian children and adolescents. These associations interacted with BMI and birth weight.

SUBMITTER: Heidari-Beni M

PROVIDER: S-EPMC4764108 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Interaction of cholesterol ester transfer protein polymorphisms, body mass index, and birth weight with the risk of dyslipidemia in children and adolescents: the CASPIAN-III study.

Heidari-Beni Motahar M Kelishadi Roya R Mansourian Marjan M Askari Gholamreza G

Iranian journal of basic medical sciences 20151101 11

<h4>Objectives</h4>This study aims to investigate joint association between cholesterol ester transfer protein (CETP) polymorphisms and body mass index (BMI) or birth weight with the risk of dyslipidemia in Iranian children and adolescents.<h4>Materials and methods</h4>This study was conducted as a sub-study of the "school-based nationwide health survey" (CASPIAN-III). We randomly selected 750 samples from the whole blood samples. Real-time PCR and high resolution melt (HRM) analysis were perfor ...[more]

PMID: 26949494

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Project description:Cholesteryl ester transfer protein (CETP) inhibitors are gaining substantial research interest for raising high density lipoprotein cholesterol levels. The aim of the research was to estimate the efficacy and safety of cholesteryl ester transfer protein inhibitors as novel lipid modifying drugs. Systematic searches of English literature for randomized controlled trials (RCT) were collected from MEDLINE, EBASE, CENTRAL and references listed in eligible studies. Two independent authors assessed the search results and only included the double-blind RCTs by using cholesteryl ester transfer protein inhibitors as exclusively or co-administrated with statin therapy irrespective of gender in enrolled adult subjects. Two independent authors extracted the data by using predefined data fields. Of 503 studies identified, 14 studies met the inclusion criteria, and 12 studies were included into the final meta-analysis. Our meta-analysis revealed that CETP inhibitors increased the HDL-c levels (n = 2826, p<0.00001, mean difference (MD) = 20.47, 95% CI [19.80 to 21.15]) and total cholesterol (n = 3423, p = 0.0002, MD = 3.57, 95%CI [1.69 to 5.44] to some extent combined with a reduction in triglyceride (n = 3739, p<0.00001, MD = -10.47, 95% CI [-11.91 to -9.03]) and LDL-c (n = 3159, p<0.00001, MD = -17.12, 95% CI [-18.87 to -15.36]) irrespective of mono-therapy or co-administration with statins. Subgroup analysis suggested that the lipid modifying effects varied according to the four currently available CETP inhibitors. CETP inhibitor therapy did not increase the adverse events when compared with control. However, we observed a slight increase in blood pressure (SBP, n = 2384, p<0.00001, MD = 2.73, 95% CI [2.14 to 3.31], DBP, n = 2384, p<0.00001, MD = 1.16, 95% CI [0.73 to 1.60]) after CETP inhibitor treatment, which were mainly ascribed to the torcetrapib treatment subgroup. CETP inhibitors therapy is associated with significant increase in HDL-c and decrease in triglyceride and LDL-c with satisfactory safety and tolerability in patients with dyslipidemia. However, the side-effect on blood pressure deserves more consideration in future studies.

Project description:AimsLow-density lipoprotein (LDL-C) lowering is imperative in cardiovascular disease prevention. We aimed to compare accuracy of three clinically-implemented LDL-C equations in a clinical trial of cholesterol ester transfer protein (CETP) inhibition.Methods and resultsMen and women aged 18-75 years with dyslipidaemia were recruited from 17 sites in the Netherlands and Denmark. Patients were randomly assigned to one of nine groups using various combinations of the CETP inhibitor TA-8995 (obicetrapib), statin therapy, and placebo. In pooled measurements over 12 weeks, we calculated LDL-C by the Friedewald, Martin/Hopkins, and Sampson equations, and compared values with preparative ultracentrifugation (PUC) LDL-C overall and with a special interest in the low LDL-C/high triglycerides subgroup. There were 242 patients contributing 921 observations. Overall median LDL-C differences between estimates and PUC were small: Friedewald, 0.00 (25th, 75th: -0.10, 0.08) mmol/L [0 (-4, 3) mg/dL]; Martin/Hopkins, 0.02 (-0.08, 0.10) mmol/L [1 (-3, 4) mg/dL]; and Sampson, 0.05 (-0.03, 0.15) mmol/L [2 (-1, 6) mg/dL]. In the subgroup with estimated LDL-C <1.8 mmol/L (<70 mg/dL) and triglycerides 1.7-4.5 mmol/L (150-399 mg/dL), the Friedewald equation underestimated LDL-C with a median difference versus PUC of -0.25 (-0.33, -0.10) mmol/L [-10 (-13, -4) mg/dL], whereas the median difference by Martin/Hopkins was 0.00 (-0.08, 0.10) mmol/L [0 (-3, 4) mg/dL] and by Sampson was -0.06 (-0.13, 0.00) mmol/L [-2 (-5, 0) mg/dL]. In this subgroup, the proportion of LDL-C observations <1.8 mmol/L (<70 mg/dL) that were correctly classified compared with PUC was 71.4% by Friedewald vs. 100.0% by Martin/Hopkins and 93.1% by Sampson.ConclusionIn European patients with dyslipidaemia receiving a CETP inhibitor, we found improved LDL-C accuracy using contemporary equations vs. the Friedewald equation, and the greatest accuracy was observed with the Martin/Hopkins equation.RegistrationClinicalTrials.gov, NCT01970215.

Dataset Information

Interaction of cholesterol ester transfer protein polymorphisms, body mass index, and birth weight with the risk of dyslipidemia in children and adolescents: the CASPIAN-III study.

Publications

Interaction of cholesterol ester transfer protein polymorphisms, body mass index, and birth weight with the risk of dyslipidemia in children and adolescents: the CASPIAN-III study.

Similar Datasets

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