6 research outputs found
Genetic polymorphisms of the SHBG gene can be the effect on SHBG and HDL-cholesterol levels in Coronary Heart Disease: a case-control study
No full textAkadam Teker, Aysegul Basak/0000-0003-3618-0560WOS: 000478684300060PubMed: 31111369Sex hormone binding globulin (SHBG) level is positively associated with the high-density lipoprotein cholesterol (HDL-C) levels. The aim of this study was to investigate the effects of the SHBG gene variations (D356N, rs1799941, and P156L) on SHBG and HDL-C levels and Coronary Heart Disease (CHD) risk. The SHBG D356N (rs6259,G>A), P156L (rs6258,C>T), and rs1799941(G>A) polymorphisms were determined in 131 male CHD patients and 55 male controls by PCR-RFLP and real-time PCR techniques. SHGB levels were measured by Electro-chemiluminescence immunoassay (ECLIA). In the patients who had SHBG levels lower than threshold 35nmol/l value, the risk of being HDL-C levels lower than threshold 0.90mmol/l value was observed statistically significant (p=0.017; OR 2.522, 95% CI 1.170-5.438). The rs1799941 GG was associated with increased CHD risk when compared with the A allele carriers (GA+AA) (p=0.019, OR 2.222, 95% CI 1.130-4.371). In addition, the rs1799941 GG genotype and D356NN allele were associated with lower SHBG in the CHD group (p<0.01). The logistic regression analysis also revealed the rs1799941 GG genotype was significantly associated with low SHBG in CHD patients. It was observed that Haplotype-1(rs1799941 G allele-P156L P allele-D356N D allele) was associated with increased CHD risk, while Haplotype-2 (rs1799941 rare A allele-P156L C allele- D356N G allele) was correlated with the decreased CHD risk (p=0.0167). Our findings suggest that there is a positive correlation between SHBG and HDL-C levels in CHD patients, and this association might be affected by SHBG gene variations.Research Fund of Istanbul UniversityIstanbul University [12104]The present work was supported by the Research Fund of Istanbul University. Project No. 12104. The authors would like to thank Professor Oguz Ozturk and Associate Professor Ozlem Kucukhuseyin for their statistical contribution and valuable comments and suggestions, which were helpful in improving the paper
BMP1 5'UTR+104 T/C gene variation: can be a predictive marker for serum HDL and apoprotein A1 levels in male patients with coronary heart disease
No full textAkadam Teker, Aysegul Basak/0000-0003-3618-0560; Ozturk, Oguz/0000-0002-2439-9269WOS: 000444752900058PubMed: 30062502Apolipoprotein A1 (Apo A1), the major protein of HDL, is secreted as a proprotein and then is cleaved by C-terminal procollagen endoproteinase/bone morphogenetic protein-1 (BMP1). BMP1 stimulates the conversion of newly secreted proapo A1 to its phospholipid-binding form. Therefore, genetic variations of BMP1 gene may affect serum ApoA1 and HDL levels. We aimed to investigate the effects of the functional 5'UTR + 104 (T/C) variant of BMP1 on serum ApoA1 and HDL levels and risk of coronary heart disease (CHD) in this study. The BMP1 5'UTR + 104 (T/C) (rs143383) variation was determined in 131 male patients with CHD and 51 male controls by real-time polymerase chain reaction technique. ApoA1 levels were measured by immunoturbidimetry. The serum Apo-A1 levels were found higher in controls with the BMP1-CC genotype than those with the T-allele (p < 0.001). Our findings show the association of this variation with serum ApoA1 and HDL-C levels which increase in the order of CT < TT < CC in the controls. No effect was found on ApoA1 and HDL-C levels in CHD patients, as it was observed in the controls. However, the BMP1-TT genotype was associated with higher triglyceride (TG) levels as compared to C-allele (p = 0.009). These discrepancies could be due to statin therapy which has dominant effects on lowering cholesterol levels comparing to TG levels. Our results indicated that the BMP1 5'UTR + 104 (T/C) variation may affect the serum ApoA1 and lipoprotein levels depending on statin therapy so that contributes to the development of CHD.Scientific Research Projects Coordination Unit of Istanbul UniversityIstanbul University [11304]The present study was supported by a grant from the Scientific Research Projects Coordination Unit of Istanbul University (Project No: 11304)
Effects of the Variants of Activin Receptor-like Kinase-1 and 2 on the Lipid Profile of Patients with Coronary Heart Disease
No full textIntroduction: Coronary heart disease (CHD) due to atherosclerosis is a multifactorial disease with high morbidity caused by interaction of various genetic and environmental factors. Hyperlipidemia which is accepted as the most important risk factor for atherosclerosis; characterized by high concentration of low density lipoprotein (LDL)-cholesterol (LDL-C) and low concentration of high density lipoprotein (HDL)-cholesterol (HDL-C). Epidemiological studies prove the inverse relationship between HDL-C levels and CHD. Apolipoprotein A1, the major protein of HDL, is secreted as proprotein and then cleaved by C-terminal procollagen endoproteinase/bone morphogenetic protein-1 (BMP-1). Reporting of the role of BMP receptors in lipoprotein metabolism indicates that variations in these genes may be important. However, there are no studies in the literature about the variations in type I receptors for activin receptor-like kinase (ALK) 1 and ALK2 and its effects on lipid profile. In this study, it was aimed to determine the role of the gene variants of ALK1 (Q292P ve S333G) and ALK2 (R206H) receptors in the development of CHD and their effects on serum lipoprotein levels.
Methods: This study was carried out using a sample of 131 patients with CHD and 51 controls. ALK1 and ALK2 genotypes were determined by real-time polymerase chain reaction and technique.
Results: Genotype distributions of ALK1 and ALK2 were the same between the study groups (p>0.05). Mutations in ALK1 and ALK2 were observed only in the patient group. ALK1 Q292P mutation and ALK2 R206H mutation exerted positive effects on the serum lipid profile.
Conclusion: The findings of our study suggested that mutations of ALK1 and ALK2 genes may contribute to antiatherogenic lipid profile and may protect against the development of CHD.Supported by Istanbul University Scientific Research Projects Unit (no: 11304)
Aberrant Activation-Induced Cytidine Deaminase Gene Expression Links BCR/ABL1-Negative Classical Myeloproliferative Neoplasms
No full textPrognostic Significance Of ASXL1 and IDH Mutations inPhiladelphia Negative Myeloproliferative Neoplasms
No full textEvaluation of the Effect of NQO1 C609T (rs1800566) Gene Variations in Philadelphia-negative Myeloproliferative Neoplasms in Turkish Population
No full textWOS: 000512371600003Introduction: Philadelphia-negative myeloproliferative neoplasm (MPN) is a hematopoietic stem cell disorder consisting of essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) associated with myeloid cell proliferation without differentiation and maturation defects. It is characterized by hypercellular bone marrow and an increase in one or more cell lines in the peripheral blood. In the hematopoietic stem cell, Janus kinase 2 (JAK2), which is a cytoplasmic tyrosine kinase, remains constantly phosphorylated (active) as a result of the V617F somatic mutation in the pseudokinase region. Even if the phosphorylated JAK2 does not receive a stimulus, it performs signal transmission and causes continuous gene expression. This explains the excessive increase in one or more blood cell lines. NAD(P)H quinone oxidoreductase-1 (NQO1) is a phase 1 enzyme that prevents the formation of reactive and toxic semiquinone metabolites by reducing two electrons in one step. The C609T polymorphism of the NQO1 gene leads to loss of enzyme activity due to the enzyme becoming unstable. While enzyme activity is not observed in individuals with both mutant alleles, moderate activity is observed in heterozygous individuals. Studies have reported a relationship between NQO1 C609T polymorphism and various cancer types. In our study, it was aimed to investigate the possible relationship between NQO1 C609T polymorphism and MPN development. Methods: Our study group consisted of 119 MPN patients and 122 healthy controls. DNA isolation was performed from peripheral blood taken from the study groups. The JAK2 V617F mutation was detected using Real-time polymerase chain reaction (PCR), and NQO1 C609T gene polymorphism was detected using the PCR- restriction fragment length polymorphism method. SPSS 21.0 was used for statistical analysis. Results: No statistically significant difference was found between the patient and control groups in terms of NQO1 genotype distributions (p>0.05). When cases with ET, PMF, and PV were compared in terms of frequency of JAK2 V617F mutation, the rate in PV was higher (respectively; 62.5%, 61.5%, 78.6%). There was no relationship between JAK2 mutation positivity and NQO1*2 polymorphism. Conclusion: According to the results obtained from our study, there is no relationship between NQO1*2 polymorphism and MPN. Variants of the NQO1 enzyme, which is essential in detoxification and activation of procarcinogens, did not increase the formation of the JAK2 V617F mutation, which is common in MPN patients. It is thought that the results should be supported by increasing the number of patient and control groups.Istanbul University Scientific Research FundIstanbul University [BAP/23924]The study was supported by the Istanbul University Scientific Research Fund (project no: BAP/23924)
