Cholesterol Ester Transfer Protein Gene Research Articles

Cholesterol Ester Transfer Protein Taq1B Polymorphism and Its Association with Cardiovascular Risk Factors in Patients Undergoing Angiography in Yazd, Eastern Iran: A Cross-Sectional Study.

Several studies assessed the relationship between the cholesterol ester transfer protein (CETP) Taq1B gene polymorphism (rs708272) with risk factors of cardiovascular diseases (CVDs). However, their findings were inconsistent. The present study investigated the relationship between CVD risk factors and the Taq1B variant in patients undergoing coronary angiography. This cross-sectional study was conducted on 476 patients aged 30-76 years old of both sexes from 2020-2021, in Yazd (Iran). The Taq1B polymorphism genotypes were evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on DNA extracted from whole blood. Standard protocols were used to measure cardio-metabolic markers. To determine the association between CVDs risk factors and the rs708272 variant, binary logistic regression was used in crude and adjusted models. Taq1B polymorphism genotype frequencies were 10.7% for B1B1, 72.3% for B1B2, and 17% for B2B2. There was no significant association between abnormal levels of CVDs risk factors and different genotypes of the Taq1B variant, Gensini score (P=0.64), Syntax score (P=0.79), systolic blood pressure (P=0.55), diastolic blood pressure (P=0.58), and waist circumference (P=0.79). There was no significant association between genotypes of the rs708272 variant and any abnormal serum lipid levels. After adjusting for confounders, the results remained non-significant. There was no significant association between CVDs risk factors and CETP rs708272 polymorphism. The relationship between CETP gene variants and CVD occurrences varied across groups, implying that more research in different regions is required.A preprint version of this manuscript is available at https://www.researchsquare.com/article/rs-2575215/v1 with doi: 10.21203/rs.3.rs-2575215/v1.

Association of the polymorphisms of the cholesteryl ester transfer protein gene with coronary artery disease: a meta-analysis.

This meta-analysis aimed to assess the association of the polymorphisms of cholesterol ester transfer protein (CETP) rs708272 (G>A), rs5882 (G>A), rs1800775 (C>A), rs4783961 (G>A), rs247616 (C>T), rs5883 (C>T), rs1800776 (C>A), and rs1532624 (C>A) with coronary artery disease (CAD) and the related underlying mechanisms. A comprehensive search was performed using five databases such as PubMed, EMBASE, Web of Science, Cochrane Library and Scopus to obtain the appropriate articles. The quality of the included studies was assessed by the Newcastle-Ottawa Scale. The statistical analysis of the data was performed using STATA 17.0 software. The association between CETP gene polymorphisms and risk of CAD was estimated using the pooled odds ratio (OR) and 95% confidence interval (95% CI). The association of CETP gene polymorphisms with lipids and with CETP levels was assessed using the pooled standardized mean difference and corresponding 95% CI. P < 0.05 was considered statistically significant. A total of 70 case-control studies with 30,619 cases and 31,836 controls from 46 articles were included. The results showed the CETP rs708272 polymorphism was significantly associated with a reduced risk of CAD under the allele model (OR = 0.846, P < 0.001), the dominant model (OR = 0.838, P < 0.001) and the recessive model (OR = 0.758, P < 0.001). AA genotype and GA genotype corresponded to higher high-density lipoprotein cholesterol (HDL-C) concentrations in the blood compared with GG genotype across the studied groups (all P < 0.05). The CETP rs5882 and rs1800775 polymorphisms were not significantly associated with CAD under the allele model (P = 0.802, P = 0.392), the dominant model (P = 0.556, P = 0.183) and the recessive model (P = 0.429, P = 0.551). Similarly, the other mentioned gene polymorphisms were not significantly associated with CAD under the three genetic models. The CETP rs708272 polymorphism shows a significant association with CAD, and the carriers of the allele A are associated with a lower risk of CAD and higher HDL-C concentrations in the blood compared to the non-carriers. The CETP rs5882, rs1800775, rs4783961, rs247616, rs5883, rs1800776, and rs1532624 are not significantly associated with CAD. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432865, identifier: CRD42023432865.

ПОЛИМОРФИЗМ RS247616 ГЕНА CETP У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ И ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА: ОСОБЕННОСТИ ЛИПИДНОГО ОБМЕНА И ЭФФЕКТИВНОСТИ ТЕРАПИИ СТАТИНАМИ

Abstract. Introduction. Dyslipidemia is a modifiable risk factor for cardiovascular complications in patients with chronic ischemia-induced heart failure. Being the best-known class of drugs, statins effectively reduce cardiovascular mortality in all age groups. Effectiveness of using lipid-lowering drugs is determined by some factors, including genetic ones. Polymorphism rs247616 of the CETP (cholesterol ester transfer protein) gene is associated with changing high-density lipoprotein levels in blood serum. Aim. To analyze the clinical parameters and effectiveness of lipid-lowering therapy in stable chronic ischemia-induced heart failure patients with the rs247616 polymorphism of the CETP gene. Materials and Methods. We examined 517 patients with chronic ischemia-induced heart failure, aged 66.4±10.4 years, of both sexes. A genetic control of 118 conditionally healthy individuals was included. We analyzed the allele frequency of the CETP rs247616 occurrences, clinical characteristics, statin administration frequency, dose range, and achieving the lipid metabolism goals, including in relation to the genotype. Results and Discussion. Statins were prescribed to 28.8% of patients with chronic heart failure, with 42.3% receiving the minimum dosage and 35.6% receiving the average therapeutic dosage. Frequency of TT-genotype and T allele of the CETP rs247616 was higher in patients with chronic heart failure compared with controls (13.2% and 10.2%, p=0.026, 35% and 26.7%, p=0.014). It was found that CC-genotype has a protective effect against the development of chronic heart failure (CC vs CT+TT, OR=0.57, 95%CI:0.38-0.86). In patients with CC-genotype chronic heart failure, a lower level of high-density lipoproteins was observed (1.12±0.37 and 1.25±0.37 mmol/l, p=0.012), as compared to the carriers of T allele (CT+TT). Percentage of individuals with total cholesterol levels below 4.5 mmol/l (33.3%, 29.7%, and 37.5%) and triglyceride levels &lt; 1.7 mmol/l (36.5%, 25%, and 37.5%) did not differ between CC-, CT-, and TT-genotypes, respectively. There is a trend towards an increase in the proportion of the carriers of T allele and TT-genotype with low-density lipoprotein levels &lt; 1.8 mmol/l (30.8%, 45.5%, and 50%) and non-high-density lipoproteins levels&lt;2.6 mmol/l (29.4%, 31.2%, and 50%). Conclusions. Effectiveness of statin therapy is low: 38.1 % of patients had the total cholesterol levels &lt; 4.5 mmol/l, 11% had low-density lipoprotein levels &lt;1.8 mmol/l, 50.6% had triglyceride levels &lt;1.7 mmol/l, and 12.2% of patients had non-high-density lipoprotein levels &lt;2.6 mmol/l. Protective effect of CC-genotype was found regarding the genesis of chronic heart failure.

Sexual Dimorphism of Atherosclerosis by Gut Microbiome in a Hyperlipidemic Diversity Outbred F1 Mouse Population

Abstract Objectives Atherosclerosis is a complex multifactorial disease that develops through the interaction of various genetic and environmental factors. The environmental factors affecting atherosclerosis susceptibility include gender differences and the gut microbiota. However, the association between sex, microbiota, and atherosclerosis remains unclear. We hypothesized that the association between gut microbial profiles and atherosclerosis demonstrates sexual dimorphism. In order to test this hypothesis, we examined atherosclerosis and microbiota in a population of hyperlipidemic outbred mice. Methods We collected offspring (262 female and 269 male mice) from a cross between hyperlipidemic male C57BL/6J mice, transgenic for both human apolipoprotein E-Leiden and cholesterol ester transfer protein genes, and ∼200 female Diversity Outbred (DO) mice, a population derived from 8 inbred strains. We fed the offspring a high fat/cholesterol diet for 12 weeks. We then examined over 20 cardio-metabolic traits and their fecal microbiota compositions using 16S rRNA sequencing. Results Female mice were significantly more susceptible to atherosclerosis with higher lesion area (P &amp;lt; 0.0001) and plasma cholesterol (P &amp;lt; 0.0001) than males. For gut microbiota analysis, females had higher microbial α-diversity (Shannon diversity, P &amp;lt; 0.0001) than males and their β-diversity (Unweighted UniFrac, R2 = 0.01, PERMANOVA &amp;lt; 0.001) showed that the overall community is significantly different. We also examined the association between sexually-dimorphic gut phylotypes and cardiometabolic phenotypes and identified a negative correlation between atherosclerosis and the abundance of the genus Bifidobacterium, while abundances of genus Lactococcus were positively associated with atherosclerosis. Upcoming studies will be designed to identify host genes affecting microbiota abundance and functional characterization of specific microbiota-atherosclerosis traits. Conclusions To the best of our knowledge, this study suggests the first example of complex interactions between sexually dimorphic traits and gut microbiota associated with atherosclerosis using DO-F1 mice. Funding Sources This work was supported by the National Heart, Lung, and Blood Institute.

Associations of systemic, serum lipid and lipoprotein metabolic pathway gene variations with polypoidal choroidal vasculopathy in China.

BackgroundTo investigate the association of systemic, serum lipids and genetic variants in the high-density lipoprotein (HDL) metabolic pathway with polypoidal choroidal vasculopathy (PCV) in China.MethodsThe case-control study was included 150 controls and 66 cases with PCV. Serum levels of total cholesterol (TC), low-density lipoprotein (LDL), HDL, triglycerides (TG), apolipoprotein A1 (APOA1), apolipoprotein B (APOB) together with systemic risk factors including gender, hyperlipidemia, diabetes mellitus (DM), hypertension, coronary artery disease (CAD) and asthma were identified. All subjects were genotyped for four single nucleotide polymorphisms (SNPs) from three genes in the HDL metabolic pathway: rs10468017 of hepatic lipase (LIPC), rs12678919 of lipoprotein lipase (LPL), rs3764261 and rs173539 of cholesterol ester transfer protein (CETP) with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Student’s t-tests, chi-square tests, anova and logistic regression were used to evaluate associations.ResultsHyperlipidemia was a risk factor (odds ratio (OR) = 1.19, P = 0.001) for PCV. HDL, LDL and APOB levels were associated with PCV (OR = 0.001, P = 0.004; OR = 0.099, P = 0.010; OR = 0.839, P = 0.018). Higher level of TC was potently associated with increased risk of PCV (OR = 109.8, P = 0.000). LIPC rs10468017 was a risk factor for PCV (OR = 11.68, P = 0.000). CETP rs3764261 conferred a decreased risk for PCV (OR = 0.08, P = 0.000). No associations of LPL rs12678919 or CETP rs173539 with PCV were found. Mean level of HDL increased with T allele of the CETP gene (p = 0.026): 1.24 mmol/L (±0.31) for the GG genotype and 1.66 mmol/L (±0.54) for the TT genotype. Additionally, T allele was associated with the following increase in APOA1: 136.78 mg/dl (±20.53) for the CC genotype and 149.57 mg/dl (±22.67) for the TT genotype of LIPC and 137.91 mg/dl (±20.36) for the GG genotype and 162.67 mg/dl (±22.50) for the TT genotype of CETP gene.ConclusionOur study suggested that the significant association was found between hyperlipidemia, the serum levels of TC, HDL, LDL and APOB and PCV. The result of present study also showed that the association of LIPC rs10468017 and CETP rs3764261 with PCV.

Characteristics of Coronary Artery Disease Patients Who Have a Polymorphism in the Cholesterol Ester Transfer Protein (CETP) Gene.

Cholesterol ester transfer protein (CETP) is responsible for the transformation of high density lipoprotein (HDL) to low density lipoprotein (LDL) and is a risk factor for atherosclerosis. Our study investigated the association of the rs5883 CETP gene polymorphism with HDL and LDL levels, in 45 coronary artery disease patients and 45 control patients. CETP gene polymorphism was detected using Real Time-Polymerase Chain Reaction (RT-PCR). Lipoprotein levels were measured using Quantimetrix system. There were lack of associaition regarding CETP polymorphism in atherosclerosis and HDL and LDL levels (p>0.05) BMI was higher among coronary artery disease patients (CADP) compared to the control group (28.97±6.38, 26.52±4.39 respectively, p<0.03). Frequency of CADP (82.6 %, n=19) who were taking treatment was higher (17.4 %, n=4) (p<0.00). The frequencies of hypertension and type-2 diabetes were higher among CADP (p<0.00). Families of CADP have more CADP (p<0.02). Small HDL particle levels were higher in the control group (p<0.00). In Turkey, BMI, and frequencies of hypertension and type-2 diabetes were higher among CADP than among healthy controls. Furthermore, the genotypes of the rs5883 CETP gene polymorphism did not differ between CADP and healthy controls.

The polymorphism of cholesterol ester transfer protein gene and lipid profile in men with coronary atherosclerosis

The polymorphism of cholesterol ester transfer protein gene and lipid profile in men with coronary atherosclerosis

Liver X Receptor Gene Expression is Enhanced in Children with Obstructive Sleep Apnea-Hyperpnoea Syndrome and Cyclooxygenase-2 (COX-2) is Correlated with Severity of Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS).

BackgroundLiver X receptor (LXR) is a nuclear receptor presenting in macrophages; it works indispensably in lipid metabolism control and also negatively regulates the expression of inflammatory genes in macrophages. There are many LXR-related studies in adults with metabolic syndrome but rare reports in obese children with obstructive sleep apnea-hypopnea syndrome (OSAHS). The aim of this study was to investigate the expression of LXR, cholesterol ester transfer protein (CETP), and cyclooxygenase-2 (COX-2) genes in obese children with OSAHS compared with obese children without OSAHS and non-obese children.Material/MethodsSleep monitoring was conducted in 80 obese children with sleep disorders. Fasting morning blood samples from the 80 obese children and 51 normal children were collected and separated, so that macrophages were obtained after culture. Fluorescence quantitative real-time PCR (RT-PCR) was used to detect expression levels of the LXR, CETP, and COX-2 genes.ResultsLXR, COX-2, and CETP levels in the OSAHS group were higher than those in the other two groups (P<0.05), and the LXR levels in the group of obese children without OSAHS were higher than those in control group (P<0.05). COX-2 expression in the group with moderate to severe OSAHS was higher than that in the group with mild OSAHS (P<0.05). Meanwhile, there were no significant differences in the LXR and CETP levels between the moderate to severe OSAHS group and the mild OSAHS group (P>0.05).ConclusionsLXR gene expression was significantly increased in obese children with OSAHS. The severity of OSAHS was positively correlated with COX-2 levels.

The Cholesteryl Ester Transfer Protein (CETP) Taqib and I405V Gene Polymorphisms and Statin Treatment

Background: CETP (cholesterol ester transfer protein) is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It is composed mainly at the liver and it collects triglycerides from chylomicrons and VLDL and exchanges them for cholesteryl esters from HDL. By this mean, very dense LDL molecules are being formed. The latter are very atherogenetic factors. The gene encoding CETP is located on the long (q) arm of chromosome 16 at position 21. It has been found that at least two polymorphisms in this gene, TaqIB (with B1B1, B1B2 and B2B2 genotypes) and I405V (with II, IV and VV genotypes), have been associated with different response to statin treatment. Aim: The aim of this study was to investigate a probable correlation of the aforementioned CETP gene polymorphisms with better or worse response to two specific statins: simvastatin and atorvastatin. Methods: The DNA of 78 subjects, 53 men (67.9%) and 25 women (32.1%) of mean age 57±20 years with dyslipidemia, was analyzed for the different genotypes of the CETP gene polymorphisms TaqIB and I405V. To all these patients simvastatin and atorvastatin were administered as lipid lower agents and they had a lipid profil test four times during the study period. Namely, before the beginning of the therapy, two months after taking the first statin (either simvastatin or atorvastatin), two months after they quitted therapy and last time two months after restarting the lipid lower therapy with the other statin. Results: Both statins administered to patients succeeded to reduce significantly total cholesterol, triglycerides and LDL-C levels and simultaneously to augment significantly HDL-C levels. These changes have been observed in all patients independently of their genotype of the two studied CETP gene polymorphisms. No significant differences were demonstrated in total cholesterol, triglycerides, HDL-C and LDL-C levels before and after simvastatin and atorvastatin therapy across Taq1B and I405V genotypes. Moreover, the effect of age and gender on lipid levels, independently of which statin was used or the genotype, was not significant. Conclusion: The initial hypothesis of our study, that there is a probable correlation between different genotypes of TaqIB and I405V CETP gene polymorphisms and response to treatment with simvastatin and atorvastatin was not confirmed.

Additive Antiatherogenic Effects of CETP rs708272 on Serum LDL Subfraction Levels in Patients with CHD Under Statin Therapy.

Recently, subfraction analysis of serum low density lipoprotein (LDL) is considered to be a better predictor of the risk of coronary heart disease (CHD) compared to the other lipid parameters. The aim of this study was to examine the effects of the HDL-associated Taq1B (rs708272) SNP of cholesterol ester transfer protein (CETP) gene on serum LDL subfractions in patients with CHD. Serum lipid levels were measured enzymatically and LDL subfraction analysis was carried out by the Lipoprint System (Quantimetrix, CA, USA). The CETP rs708272 SNP was studied in 66 healthy controls and 79 patients with CHD receiving statin therapy by the PCR-RFLP technique. The CHD patients had elevated antiatherogenic LDL-1 subfraction (p=0.042), decreased atherogenic IDL-C subfraction (p=0.023), and total IDL (p=0.030) levels compared to the healthy controls. The CETP rs708272 Taq1B minor B2 allele was associated with increased levels of antiatherogenic LDL-1 (B2: 0.40±0.20 vs. B1B1: 0.25±0.08, p=0.004) and large-LDL (LDL 1-2) subfractions in the CHD group (B2 allele: 0.68±0.41 vs. B1B1: 0.42±0.20; p<0.05), while it was associated with reduced levels of the large-LDL subfraction in healthy subjects (B2 allele: 0.29±0.14 vs. B1B1: 0.54±0.24; p=0.017). However, there was no statistically significant association between the CETP rs708272 SNP and small dense LDL subfraction (LDL 3-7) and lipoprotein levels (p>0.05). Our findings have indicated that the CETP rs708272 SNP together with statin therapy may show a favorable effect on antiatherogenic LDL-1 and large-LDL subfractions in CHD patients with an atherogenic effect on large-LDL subfraction in healthy subjects. Based on these results, it can be concluded that the effects of the CETP variation on LDL subfraction could change in cardiometabolic events such as CHD and statin therapy.

Impact of variants in CETP and apo AI genes on serum HDL cholesterol levels in men and women from the Polish population.

IntroductionPolymorphisms in the cholesterol ester transfer protein (CETP) gene and apolipoprotein AI (apo AI) gene are identified as the most common genetic factors influencing high-density lipoprotein cholesterol (HDL cholesterol) levels. Low HDL cholesterol is an important risk factor for cardiovascular disease. We investigated the effect of the TaqIB polymorphism of the CETP gene and the 75G/A polymorphism of the apo AI gene on the HDL cholesterol concentration in a sample of Polish adults.Material and methodsA total of 621 subjects, 414 women and 207 men, were included in this study. Lipid levels were measured using standard protocols, and apolipoprotein AI was determined by immunoturbidimetric assay. CETP and apo AI genotyping was performed using a restriction fragment length polymorphism based method.ResultsSignificantly lower HDL cholesterol concentrations were found in B1B1 homozygotes than in carriers of the B2 allele of the TaqIB polymorphism in the CETP gene among both men and women. In GG homozygotes of the 75G/A polymorphism in the apo AI gene lower HDL cholesterol levels were observed, but the difference did not reach statistical significance. A statistically significant association of low HDL cholesterol (< 25th percentile) with CETP genotypes was found in women (p < 0.0001) and in men (p = 0.0368).ConclusionsThese data demonstrate a significant impact of the TaqIB polymorphism in the CETP gene on HDL cholesterol levels in the studied Polish population, while the effect of the 75G/A polymorphism in the apo AI gene appears not to be significant.

Newer perspectives of coronary artery disease in young

Coronary artery disease (CAD) occurring in less than 45 years of age is termed as young CAD. Recent studies show a prevalence of 1.2% of CAD cases in this age group. Ethnic wise south Asians especially Indians are more vulnerable to have CAD in young age group with a prevalence of 5% to 10%. Conventional risk factors such as smoking, diabetes, hypertension, obesity and family history seems to be as important as in older CAD subjects. But the prevalence of these risk factors seems to vary in younger subjects. By far the most commonly associated risk factor is smoking in young CAD. Several genes associated with lipoprotein metabolism are now found to be associated with young CAD like cholesterol ester transfer protein (CETP) gene, hepatic lipase gene, lipoprotein lipase gene, apo A1 gene, apo E gene and apo B. Biomarkers such as lipoprotein (a), fibrinogen, D-dimer, serum Wnt, gamma glutamyl transferase, vitamin D2 and osteocalcin are seems to be associated with premature CAD in some newer studies. In general CAD in young has better prognosis than older subjects. In terms of prognosis two risk factors obesity and current smoking are associated with poorer outcomes. Angiographic studies shows predominance of single vessel disease in young CAD patients. Like CAD in older person primary and secondary prevention plays an important role in prevention of new and further coronary events.

Association between Eight Functional Polymorphisms and Haplotypes in the Cholesterol Ester Transfer Protein (CETP) Gene and Dyslipidemia in National Minority Adults in the Far West Region of China.

We have investigated the relationship between the polymorphisms and haplotypes in the CETP gene, and dyslipidemia among the Xinjiang Kazak and Uyghur populations in China. A total of 712 patients with dyslipidemia and 764 control subjects of CETP gene polymorphism at rs12149545, rs3764261, rs1800775, rs711752, rs708272, rs289714, rs5882, and rs1801706 loci were studied by the Snapshot method, linkage disequilibrium analysis and haplotype construction. The results are as follows: (1) the minor allele of eight loci of frequencies in the two groups were different from other results of similar studies in other countries; (2) In the linear regression analysis, the HDL-C levels of rs708272 TT, rs1800775 AA, rs289714 CC and rs711752 AA genotypes were significantly higher than those of other genotypes, however, the rs3764261 GG and rs12149545 GG genotypes were significantly lower than those of other genotypes in the two ethnic groups. The HDL-C levels of the rs12149545 GG genotype were lower than those of other genotypes; (3) in the control group, the rs708272 CT genotype of TG levels were lower than in the CC genotype, the T genotype of LDL-C levels were lower than in the CC genotype, and the HDL-C levels were higher than in the CT genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype, the rs711752 AG genotype of TG levels were lower than in the GG genotype, the AA genotype LDL-C levels were lower than in the GG genotype, and the HDL-C levels were higher than in the AG genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype. In the dyslipidemia group, the rs708272 TT genotype of TC and LDL-C levels were higher than in the CT genotype and the rs3764261 TT genotype of TC levels were higher than in the GG genotype. The rs711752 AA genotype of TC and LDL-C levels were higher than in the AG genotype, and the rs12149545 AA genotype of TC and LDL-C levels were higher than in the GG genotype; (4) perfect Linkage Disequilibrium was observed for two sets of two SNPs: rs3764261 and rs12149545; rs711752 and rs708272. (5) Using SHEsis software analysis, the five A/T/A/A/T/C/A/G, A/T/A/A/T/T/G/A, G/G/A/G/C/C/G/G, G/G/C/G/C/C/A/G and G/G/C/G/C/T/G/G haplotypes were between dyslipidemia group and control group statistically significantly different (p < 0.05 in each case). The polymorphism of CETP genes rs708272, rs3764261, rs1800775, rs711752, rs12149545 was closely related to the dyslipidemia in the Xinjiang Uyghur and Kazakh ethnic groups; and the rs708272 T, rs3764261 T, rs711752 A, and rs12149545 A alleles could reduce risk of dyslipidemia in the Uyghur and Kazakh populations, however, the rs1800775 C allele showed risk factors.

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.

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. 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. 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. 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.

GW26-e2921 Lack of association between CETP I405V Polymorphism and Lipid Levels and Longevity in Guangxi Hongshui River Basin

To investigate the I405V polymorphism of the cholesterol ester transfer protein gene (CETP) and its possible association with lipid levels and longevity in Guangxi Hongshui River Basin. The polymorphism of CETP I405V locus was genotyped by PCR-RFLP and serum levels of total cholesterol (TC),

Genetic basis of dyslipidemia in disease precipitation of coronary artery disease (CAD) associated type 2 diabetes mellitus (T2DM).

Type 2 diabetes mellitus (T2DM) and its complications are linked to environmental, clinical, and genetic factors. This review analyses the disorders of lipids and their genetics with respect to coronary artery disease (CAD) associated with T2DM. Cell organelles, hepatitis C-virus infection, reactive oxygen species produced in mitochondria, and defective insulin signaling due to the arrest of G1 phase to S phase transition of β-cells have significant roles in the precipitation of the diseases. Adiponectin is anti-inflammatory and anti-atherosclerotic and improves insulin resistance. Low-density lipoprotein (LDL) is atherosclerotic, and LDL-cholesterol in T2DM is associated with high-cardiovascular risk. Further, LDL cholesterol reduction significantly reduces cardiovascular morbidity and mortality. High-density lipoprotein (HDL) is also anti-atherosclerotic due to HDL associated paraoxonase-1 serum enzyme, which prevents LDL oxidative modifications and the development of CAD. Moreover, elevated apolipoprotein B and apolipoprotein A-I (ApoB/ApoA-I) ratio in plasma is also a risk factor for CAD. LDL receptor, adiponectin, and endocannabinoid receptor-1 genes are independently associated with CAD and T2DM. Polymorphism of Apo E2 (epsilon2) is a positive factor to increase the T2DM risk and Apo E4 (epsilon4) is a negative factor to reduce the disease risk. Taq 1B polymorphism of cholesterol ester transfer protein (CETP) gene contributes to the development of atherosclerosis, whereas haplotypes of APOA5, APOC3, APOC4, and APOC5 genes are in the same cluster and are independently associated with high plasma triglyceride level, CAD and T2DM. In conclusion, because various genes, LDLR, CETP, APOA5, Apo E, Apo B, and Apo A-I, are associated with the precipitation of CAD associated with T2DM, a personalized diet-gene intervention therapy may be advocated to reduce the disease precipitation.

Taq1B CETP Polymorphism and Cardiovascular Risk in an Endogamous Pop-ulation of Diabetic Men: A Study in Santa Rosa Del Conlara, San Luis, Argentina

Objectives: Type 2 diabetes mellitus (T2DM) patients are at increased risk of cardiovascular dis- eases (CVDs). Several polymorphisms in the cholesterol ester transfer protein (CETP) gene have been reported. The aim of this study was to determine the distribution and effect of the Taq1B polymorphism in the CETP gene on clinical and biochemical indicators of CVD risk in a population of endogamous-T2DM men. Methods: 102 men (57.5 ± 9.3 years old) inhabitants of Santa Rosa del Conlara, San Luis, Argentina, were recruited and assigned into two groups (22 control and 80 T2DM). Further, these two groups were subdivided according to their Taq1B CETP gene genotypes (i.e., B1B1, B1B2 and B2B2). Clinical and fasting-plasma biochemical indicators of CVD risk were measured and their association with the B1 allele was determined. Results: Compared to control, T2DM men had more central obesity, hypertension, atherogenic index, insulin resistance and poorly controlled diabetes. Compared to T2DM men having the B2 allele, those T2DM men having the B1 allele have increased risk of CVD as assessed by systolic blood pressure (156 ± 16.0 vs 135.8 ± 19.2, p = 0.015), atherogenic index (6.15 ± 1.3 vs 4.4 ± 0.7, p = 0.0008), HDL-c levels (38.9 ± 5.3 vs 64.4 ± 8.2, p < 0.0001) and insulin resistance (HOMA-IR, 5.78 ± 3.0 vs 2.4 ± 0.78, p = 0.004). Interestingly, only body mass index (r = −0.559, p = 0.01) and HDL-c concentration (r = −0.492, p = 0.02) negatively correlated with CVD risk in the endogamous population of B1B1 and B1B2 T2DM men. Conclusion: The B1 allele of the CETP gene predicts cardiovascular complications in an * Corresponding author.

Relationship between the cholesterol ester transfer protein TaqIB polymorphism and the lipid-lowering effect of atorvastatin in patients with coronary atherosclerotic heart disease.

This study aimed to investigate the relationship between the cholesterol ester transfer protein (CETP) gene TaqIB polymorphism and the lipid-lowering effect of atorvastatin in patients with coronary atherosclerotic heart disease. Two hundred eighty-eight patients were divided into a control group, an acute coronary syndrome (ACS) group, and a stable coronary heart disease (CHD) group. Blood biochemical indices were determined using the enzyme method, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to study the TaqIB polymorphism of the CETP gene. The ACS and stable CHD groups were treated with atorvastatin, and blood lipid levels were reexamined after three months. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) were all significantly higher in the ACS and stable CHD groups compared to the control group (P < 0.05 or P < 0.01). After three months of treatment with atorvastatin, plasma levels of TC, LDL-C, triglycerides (TG) (only in patients with genotype B2B2), and lipoprotein(a) (only in patients with genotype B1B2) were all significantly decreased (P < 0.05 or P < 0.01). After treatment, the plasma level of TG was lower in patients with genotype B2B2 compared to patients with genotypes B1B1 or B1B2 (B1 carriers) (P < 0.01). Therefore, the CETP TaqIB polymorphism is associated with the lipid-lowering effect of atorvastatin in patients with CHD.

Relationship between the TaqI B polymorphism of the cholesterol ester transfer protein gene and atrial fibrillation in Han and Kazak populations

The TaqI B polymorphism in the cholesterol ester transfer protein (CETP) (B1 and B2 alleles; rs708272) is associated with changes in enzyme activity and lipid concentrations. The B1 allele of the CETP gene is a known independent risk factor for genetic susceptibility to atrial fibrillation (AF); however, little is known about this polymorphism in the minority groups of Xinjiang, China. We examined the role of this polymorphism in AF using two independent case-control studies: the Han population (101 AF patients and 129 control subjects) and the Kazak population (103 AF patients and 101 control subjects). Carriers of the B1B1 genotype were more frequent among AF patients than among controls both in the Han population (34.7 versus 26.4%; χ(2) = 10.686, P = 0.001) and in the Kazak population (53.4 versus 24.8%; χ(2) = 27.802, P < 0.001). The odds ratio (OR) for carriers of the B1B1 genotype to AF susceptibility was 0.187 [95% confidence interval (CI) = 0.071- 0.491] in the Han group and 8.426 (95%CI = 2.295-30.933) in the Kazak population. After adjustment of confounding factors such as gender, age, smoking, alcohol consumption, hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol, and high-density lipoprotein, the difference remained significant in the Han group (P = 0.001; OR = 0.187, 95%CI = 0.071-0.491) and in the Kazak group (P = 0.001; OR = 8.426, 95%CI = 2.295-30.933). The presence of the B1B1 polymorphism of the Taq1B CETP genotype contributes to the development of AF in the Han and Kazak populations in western China (Xinjiang).

Association of polymorphism of angiotensin-converting enzyme gene I/D and D442G cholesterol ester transfer protein gene with risk factors for atherosclerosis among elderly and senile patients with coronary heart disease in the republic of Sakha (Yakutia)

A comparative analysis was performed for frequency distribution of I/D polymorphism of angiotensin-converting enzyme (ACE) gene and D442G polymorphism of cholesterol ester transfer protein (CETP) gene in elderly and senile patients and long-lived patients with CHD with regard to ethnicity, age, and gender. The frequency of ACE*I/*I genotype reduces with age; the tendency towards increased proportion of ACE*D/*D genotype was observed. During the comparative analysis of ACE*D/*D and ACE*D/*I genotypes, gender differences were found in frequency of homozygous ACE*D/*D genotype. The carriers of ACE*D/D genotype were identified significantly more often among men than among women. Among all patients and especially among Yakuts, left ventricular hypertrophy confirmed by Sokolov-Lyon index for ECG was observed significantly more often in carriers of ACE*I/*I genotype. During the study of D442G polymorphism of CETP gene, the carriers of CETP*D/*G genotype were identified significantly more often among Yakuts than among nonindigenous individuals. During the comparison of frequencies of I/D polymorphism of the ACE gene, significant differences were observed with respect to body mass index (BMI) and blood lipids. In comparison of CETP*D/*D and CETP*D/*G genotypes, no significant association with CHD risk factor was found.