I405V and TaqIB polymorphisms of the cholesteryl ester transfer protein and their relation to serum lipid and lipoprotein levels in a Turkish population

Cholesteryl ester transfer protein (CETP) plays a central role in high‐density lipoprotein (HDL) metabolism. Genetic polymorphisms of the CETP gene can influence levels of serum lipoproteins. It has been reported that mean HDL‐cholesterol (HDL‐C) concentrations are low in Turkish population. Thus, we investigated the frequencies of the common I405V and TaqIB polymorphisms of the CETP gene and their relation to serum lipid and lipoprotein levels in a Turkish population. The variant allele frequencies of I405V and TaqIB polymorphisms of the CETP gene were found to be 0.38 and 0.46, respectively and similar to some of the European populations. Subjects for the VV genotype of I405V polymorphism had higher HDL‐C levels than did II subjects. The covariance analysis showed that gender and triglyceride (TG) levels have an effect on the association of HDL‐C and I405V polymorphism. In conclusion, our results indicate that I405V polymorphism may affect the HDL‐C levels in Turkish population. The association of this polymorphism and HDL‐C levels could be modified by other factors, such as gender and TG levels. Copyright © 2009 John Wiley & Sons, Ltd.     

The effect of apolipoprotein E polymorphism on plasma cholesteryl ester transfer protein activity in type 2 diabetic patients

We studied the relationship between apo E polymorphism and cholesteryl ester transfer protein (CETP) activity in 127 type 2 diabetic patients who did not take lipid lowering drugs. Furthermore, we studied the relationship between apo E and cholesteryl ester transfer protein (CETP) in modulating plasma triglyceride and HDLcholesterol. Apo E genotypes were determined by PCR-RFLP, and CETP activity was measured using an exogenous way. Our results showed that the CETP activity increased significantly in the E2 carrier group compared to E4 carriers and E3/E3 homozygous (84.7 ± 43.9 vs. 62.5 ± 35.9 vs. 52.6 ± 23.6 nmol CE/ml/2h, respectively; p = 0.015). However, there was no association between apo E polymorphism and lipid parameter variations. Even after adjustment for CETP activity, the results remained unchanged, showing that CETP did not step in the relationship between apo E and lipid parameter variations. In conclusion there is an association between apo E polymorphism and CETP activity, and this association did not affect the relationship between apo E polymorphism and triglyceride and HDLcholesterol concentrations. Published in Russian in Molekulyarnaya Biologiya, 2008, Vol. 42, No. 6, pp. 931–935. The text was submitted by the authors in English.     

Effects of cholesterol ester transfer protein Taq1B gene polymorphism on serum lipoprotein levels in Turkish coronary artery disease patients

To evaluate the effect of cholesterol ester transfer protein (CETP) Taq1B gene polymorphism on serum lipid profile in Turkish coronary artery disease (CAD) patients, we investigated Taq1B gene polymorphism of CETP and serum lipid levels in 111 controls and in 173 CAD patients with myocardial infarction. There were no significant differences in the allele distribution at this polymorphic locus between the population sample and patients with coronary artery disease with myocardial infarction. To detect the association between the Taq1B RFLP and serum lipid levels, we determined the serum concentrations of total cholesterol, triglycerides and high density lipoprotein cholesterol (HDL-C) in the subjects studied and correlated the results to the Taq1B RFLP. Patients with Taq B1B1 genotypes had lower HDL-C levels than patients with B2B2 genotype (p = 0.003). Also in control subjects with Taq B1B1 genotype, lower HDL-C levels (p = 0.05) and higher triglyceride levels (p = 0.017) and body mass index (p = 0.05) were observed compared with control subjects with the B1B2 genotype. It was observed that in our population the distribution of CETP Taq1B genotypes is similar to other populations (except Greeks). The present study demonstrates that CETP Taq1B gene polymorphism may be responsible for low HDL cholesterol levels in patients with CAD and in healthy controls in Turkey.     

Circulating microRNA profiles based on direct S-Poly(T)Plus assay for detection of coronary heart disease

Coronary heart disease (CHD) is one of the leading causes of heart-associated deaths worldwide. Conventional diagnostic techniques are ineffective and insufficient to diagnose CHD with higher accuracy. To use the circulating microRNAs (miRNAs) as non-invasive, specific and sensitive biomarkers for diagnosing of CHD, 203 patients with CHD and 144 age-matched controls (126 high-risk controls and 18 healthy volunteers) were enrolled in this study. The direct S-Poly(T)Plus method was used to identify novel miRNAs expression profile of CHD patients and to evaluate their clinical diagnostic value. This method is an RNA extraction-free and robust quantification method, which simplifies procedures, reduces variations, in particular increases the accuracy. Twelve differentially expressed miRNAs between CHD patients and high-risk controls were selected, and their performances were evaluated in validation set-1 with 96 plasma samples. Finally, six (miR-15b-5p, miR-29c-3p, miR-199a-3p, miR-320e, miR-361-5p and miR-378b) of these 12 miRNAs were verified in validation set-2 with a sensitivity of 92.8% and a specificity of 89.5%, and the AUC was 0.971 (95% confidence interval, 0.948-0.993, P < .001) in a large cohort for CHD patients diagnosis. Plasma fractionation indicated that only a small amount of miRNAs were assembled into EVs. Direct S-Poly(T)Plus method could be used for disease diagnosis and 12 unique miRNAs could be used for diagnosis of CHD.     

Meta-analyses of HFE variants in coronary heart disease

Aim

HFE gene variants can cause hereditary hemochromatosis (HH) that often comes along with an increased risk of coronary heart disease (CHD). The goal of our study is to assess the contribution of four HFE gene variants to the risk of CHD.

Methods and results

We conducted four meta-analyses of the studies examining the association between four HFE gene variants and the risk of CHD. A systematic search was conducted using MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical.

Results

Meta-analyses showed that HFE rs1799945-G allele was associated with a 6% increased risk of CHD (P = 0.02, odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01–1.11). However, no association between the other three HFE gene variants (rs1800562, rs1800730, and rs9366637) and CHD risk was observed by the meta-analyses (all P values > 0.05). In addition, the results of our case–control study indicated that rs1800562 and rs1800730 were monomorphic, and that rs1799945 and rs9366637 were not associated with CHD in Han Chinese.

Conclusions

Our meta-analysis suggested that a significant association existed between rs1799945 mutation and CHD, although this mutation was rare in Han Chinese.     

Association of cholesteryl ester transfer protein −629C > A polymorphism with high‐density lipoprotein cholesterol levels in coronary artery disease patients

In Turkish population, plasma HDL‐C levels were found to be lower than in any other country and it is suggested that this is associated with genetic origin. The cholesteryl ester transfer protein (CETP) ?629C > A polymorphism is associated with lower plasma CETP concentration, with increased HDL‐C level. In the present study, the frequency of ?629C > A polymorphism in patients with coronary artery disease (CAD) was investigated and the effect of genotype on HDL‐C was evaluated in a Turkish population. For this aim CETP ?629C > A polymorphism was studied in angiographically documented CAD patients and healthy controls. There was no statistical significance in the distribution of genotypes between patients and controls. Although A allele carriers with CAD had significantly lower HDL‐C levels than controls, plasma lipid levels showed no difference according to the genotypes. Adjustment by a logistic regression model predicting CAD status through HDL‐C and including some risk factors as covariate indicated that the HDL‐C doesn't have a significant association with CAD risk in CA and AA genotype carriers. Smoking, gender and hypertension were the common predictors for the HDL‐C levels in CA and AA carriers. Although HDL‐C appeared to be the only significant predictor of CAD in our study groups, the contribution of CETP ?629C > A polymorphism to the alterations in HDL‐C level appears to be weak to mention a protective effect of this polymorphism for CAD. In conclusion, the findings of the present study indicate that the CETP ?629C > A polymorphism is not among the determinants of the coronary artery disease in Turks. Copyright © 2009 John Wiley & Sons, Ltd.     

First survey of the three gene polymorphisms (PON1 Q192R, eNOS E298D and eNOS C-786T) potentially associated with coronary artery spasm in African populations and comparison with worldwide data

Three polymorphisms, Paraoxonase 1 (PON1) Q192R (C/G), endothelial nitric oxide synthase (eNOS) E298D (G/T) and eNOS T‐786C have been suggested to be potentially associated with coronary artery spasm in Japanese patients. Data on worldwide populations are needed to clarify whether these associations could hold true for other populations. However, few data are available especially in Africans, spasm of which has been suggested to be an aetiology of myocardial infarction. Therefore, these polymorphisms were investigated in three Africans, Ovambos (n = 123), Ghanians (n = 118) and Xhosas (n = 96), together with Japanese (n = 96), by using polymerase chain reaction‐restriction fragment length polymorphism analysis. Genotype‐distributions of all these SNPs in African populations were significantly different from those in Caucasians, whereas were similar to those in Japanese population. African populations exhibit relatively higher frequency of spasm‐associated G192 allele in PON1 Q192R being similar to Japanese population, however frequencies of spasm‐associated T298 allele and –C786 allele in SNP eNOS E298D and T‐786C, respectively, were conversely lower in Africans than Caucasians. Although healthy subjects have been recruited in this study, these findings may provide genetic background for elucidation of aetiology of spasm. Copyright © 2011 John Wiley & Sons, Ltd.     

Expression of the congenital heart disease 5/tryptophan rich basic protein homologue gene during heart development in Medaka fish,Oryzias latipes

The congenital heart disease 5 (CHD5)/tryptophan rich basic protein (WRB) is a protein containing a tryptophan‐rich carboxy‐terminal region, which was discovered in the human fetal heart. In humans, this CHD5/WRB is located between the markers ACTL5‐D21S268 within the Down syndrome (DS) Region‐2 at chromosome 21. Congenital heart disease is commonly linked to DS patients. The functions of this gene product are unknown. To identify the functions of CHD5/WRB in heart formation during embryogenesis, the medaka CHD5 cDNA (mCHD5) was isolated and its gene expression pattern and the localization of its gene product were investigated. The obtained mCHD5 belongs to the CHD5 superfamily, whose members include coiled‐coil proteins. The mCHD5 gene was found to be expressed in the developing heart after stage 28 at which the chamber (ventricle and atrium) differentiation in the heart tube is initiated in the embryo. Its gene product was also detected in the developing heart at embryonic stage 28 and 35. Knocking‐down of mCHD5 function caused severe cardiac disorder, including abnormal chamber differentiation, abnormal looping and ocular abnormality such as Cyclops. Our results provide the mCHD5 gene expression pattern as well as its physiological role during heart formation in a vertebrate model system.