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1.
Mol Biol Rep ; 49(8): 7677-7686, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35622307

RESUMO

BACKGROUND: Cardiovascular diseases are the leading cause of death worldwide, with several conditions being affected by oxidative stress. Ferroptosis, recently identified programmed cell death mechanism, is relies on oxidative stress. This study aimed to determine the expressions of the genes involved in the molecular pathways of oxidative stress and ferroptosis and the association of these genes with CAD risk factors in CAD and non-CAD individuals. METHODS AND RESULTS: The blood samples of individuals who underwent coronary angiography were collected and divided according to CAD status. Total RNA isolation was performed using the PAXgene RNA isolation kit from the whole blood samples. The mRNA expression levels of RTN3, GPX4, CAT, HMOX1, ELOVL5, SLC25A1, SLC7A11, and ACSL4 genes were determined using Real-Time PCR. Biochemical analyses were done before coronary angiography, and the results were evaluated statistically. The expression levels of the CAT gene are significantly lower in the CAD group when compared to non-CAD. HMOX1 expression levels are positively correlated with stenosis percentage, Gensini, and SYNTAX scores in the CAD group. RTN3, SLC25A1, and GPX4 mRNA expressions are correlated with HDL-C levels. Moreover, HbA1c levels and BMI, correlate negatively with ACSL4 expression in non-CAD controls. Also, ELOVL5 expression is negatively correlated with total bilirubin and direct bilirubin levels in the CAD group. CONCLUSIONS: In this study, the genes related to oxidative stress and ferroptosis were found associated with biochemical parameters associated with CAD risk. These preliminary results may provide a new perspective to further studies investigating the reasons behind the identified associations.


Assuntos
Doença da Artéria Coronariana , Ferroptose , Transportadores de Ânions Orgânicos , Bilirrubina , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/genética , Humanos , Proteínas Mitocondriais , RNA , RNA Mensageiro/genética , Fatores de Risco
2.
Turk Kardiyol Dern Ars ; 50(1): 22-33, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35197230

RESUMO

OBJECTIVE: Coronary artery disease (CAD) is an important public health problem worldwide. Therefore, it is important to identify the molecular mechanisms and the candidate gene polymorphisms involved in the development of CAD. In this study, we focused on 2 polymorphisms of the atherosclerosis-related genes, ESR1 and CYP19A1. METHODS: Unselected 339 individuals who underwent coronary angiography were divided into 2 groups: those with normal coronary arteries (≤30% stenosis) and those with critical disease (≥50% stenosis). Individuals were genotyped for CYP19A1 rs10046 C/T and ESR1 rs2175898 A/G polymorphisms using hybridization probes in real-time PCR. In addition, Gensini and SYNTAX scores were assessed. RESULTS: ESR1 polymorphism was significantly associated with CAD in men (p=0.036) via G allele carriage. Multiple logistic regression analyses showed that ESR1 rare allele carriage was associated with CAD presence (Odds ratio=2.12, 95% confidence interval 1.01-4.1, p=0.025), adjusted for age, HDL-C, LDL-C and smoking status in the male group. CYP19A1 rs10046 T allele carriers had a 2.84-fold increased risk for complex CAD in multiple logistic regression analysis (p=0.016). Furthermore, the univariate analysis of variance indicated that T allele carriage of rs10046 polymorphism was associated with increased SYNTAX and Gensini scores (p<0.05). Female patients who were ESR1 G allele carriers with CAD had higher adiponectin levels (p=0.005), whereas HbA1c levels were associated with T allele of CYP19A1 in the CAD group (p=0.004) and male CAD group (p=0.018). CONCLUSION: The CYP19A1 and ESR1 polymorphisms were associated with the presence and severity of CAD. These gene polymorphisms warrant further studies for the elucidation of their contribution to CAD development.


Assuntos
Doença da Artéria Coronariana , Alelos , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Feminino , Predisposição Genética para Doença , Hormônios Esteroides Gonadais , Humanos , Masculino , Polimorfismo Genético , Fatores de Risco
3.
Turk Kardiyol Dern Ars ; 50(1): 34-45, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35197231

RESUMO

OBJECTIVE: Intelectin-1 is an anti-inflammatory adipokine encoded by the Intelectin 1 (ITLN1) gene. Genetic variations in the ITLN1 gene affect the risk of coronary artery disease (CAD) and related CAD risk factors. In this study, we aimed to investigate whether the ITLN1 gene Val109Asp polymorphism has an effect on the severity of CAD and serum lipid levels in both men and women. METHODS: A total of 493 subjects who underwent coronary angiography (43.5% women, mean age 63.1±9.5 years) were grouped as individuals with critical CAD (≥70% stenosis, n=202), non-critical CAD (31%-69% stenosis, n=90), and non-CAD (control group) (1%-30% stenosis, n=201). Genotyping was performed using LightSNiP assay in Real-Time PCR. RESULTS: The frequency of the Val allele was significantly different among all the patients with critical CAD (n=41) and non-CAD control (n=51) groups in women (p=0.033) but not in men (n=77 and n=38). Women with the Val allele had a 1.69-fold increased risk for critical CAD (p=0.033). In addition, the presence of Val allele was associated with higher coronary stenosis after adjustment for several confounders only in women with critical CAD (p=0.025). Furthermore, carriers of the Val allele exhibited an increased low-density lipoprotein cholesterol (LDL-C) in men with critical CAD than in those with non-CAD (p<0.05). CONCLUSION: These results suggest that the Val allele of the ITLN1 Val109Asp polymorphism is associated with critical CAD and high LDL-C levels in our study population. Further studies are required to elucidate the effect of Val109Asp polymorphism on CAD pathogenesis.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Citocinas/genética , Lectinas/genética , Idoso , Alelos , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/epidemiologia , Feminino , Proteínas Ligadas por GPI/genética , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco
4.
J Diabetes Complications ; 36(1): 108078, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34686405

RESUMO

AIMS: Coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) are important and increasing public health problems. This study aimed to identify the impact of APOE and CLU gene polymorphisms on the prevalence of both diseases, along with the effect of these polymorphisms on lipid profile and glucose metabolism. METHODS: 736 CAD patients (≥50 stenosis) and 549 non-CAD subjects (≤30 stenosis) were genotyped for APOE (rs429358 and rs7412) and CLU (rs11136000) gene polymorphisms using hydrolysis probes in real-time PCR. Blood samples of the individuals were drawn before coronary angiography and biochemical analyses were done. The associations between the polymorphisms and the selected parameters were assessed using statistical analysis. RESULTS: In this study, the ε2 and ε4 isoforms of apoE were associated with serum lipid levels and TC/HDL-C and LDL-C/HDL-C ratios in analysis adjusted for several confounders and in crude analysis. It was observed that CLU T allele carrier non-CAD subjects had lower glycosylated hemoglobin levels. Furthermore, the effects of APOE and CLU polymorphisms were assessed on CAD and T2DM presence. In crude and multiple logistic regression analyses, the ε2 isoform carriers had a lower risk for CAD complexed with T2DM. When the combinational effects of APOE and CLU polymorphisms were examined, the ε2 and T allele carriers had decreased risk for CAD complexed with T2DM compared to non-carriers. CONCLUSIONS: In conclusion, the combination of APOE and CLU polymorphisms is associated with CAD-DM status along with the APOE ε2 isoform by itself, and the apoE isoforms are strongly associated with serum lipid levels.


Assuntos
Apolipoproteínas E , Clusterina , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Apolipoproteínas E/genética , Clusterina/genética , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único
5.
Mol Biol Rep ; 48(12): 7719-7732, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34689283

RESUMO

BACKGROUND: Although patients with coronary artery disease (CAD) have a high mortality rate, the pathogenesis of CAD is still poorly understood. During the past decade, microRNAs (miRNAs) have emerged as new, potential diagnostic biomarkers in several diseases, including CAD. This study aimed to investigate the expression profiles of miRNAs in individuals with CAD and non-CAD. METHODS AND RESULTS: The Agilent's microarray analyses were performed to compare the whole blood miRNA profile of selected individuals with severe CAD (n = 12, ≥ 90% stenosis) and non-CAD (n = 12, ≤ 20 stenosis). Expressions of selected differentially expressed miRNAs (DEMs) were analyzed for validation in individuals with critical CAD (n = 50) and non-CAD (n = 43) using real-time PCR. Target prediction tools were utilized to identify miRNA target genes. We identified 6 DEMs that were downregulated in CAD patients, which included hsa-miR-18a-3p and hsa-miR-130b-5p, that were analyzed for further testing. Expression levels of hsa-miR-130b-5p were found negatively correlated with SYNTAX score and stenosis in female CAD patients (p < 0.05). In addition, both miRNAs were found positively correlated with plasma HDL and inversely correlated with fasting triglyceride levels (p < 0.05). In linear regression analysis adjusted for several confounders, the correlations have remained statistically significant. Computational prediction of target genes indicated a relevant role of hsa-miR-130b-5p and hsa-miR-18a-3p in modulating the expression of genes associated with cardiovascular diseases. CONCLUSION: Our findings highlight a significantly different pattern of miRNA expression in CAD patients in microarray results. Hsa-miR-18a-3p and hsa-miR-130b-5p might serve as biomarkers of CAD development and progression and warrant further attention.


Assuntos
Doença da Artéria Coronariana/genética , MicroRNAs/genética , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , MicroRNAs/análise , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transcriptoma/genética , Turquia
6.
Mol Biol Rep ; 48(5): 3945-3954, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34021444

RESUMO

Coronary artery disease (CAD) which is a complex cardiovascular disease is the leading cause of death worldwide. The changing prevalence of the disease in different ethnic groups pointing out the genetic background of CAD. In this study, we aimed to evaluate the contribution of selected cholesterol metabolism-related gene polymorphisms to CAD presence. A total of 493 individuals who underwent coronary angiography were divided into 2 groups: normal coronary arteries (≤ 30% stenosis) and critical disease (≥ 50% stenosis). Individuals were genotyped for APOC1 (rs11568822), APOD (rs1568565), LIPA (rs13500), SORL1 (rs2282649), and LDLR (rs5930) polymorphisms using hydrolysis probes in Real-Time PCR. Blood samples were drawn before coronary angiography and biochemical analyses were done. The results were statistically evaluated. When the study group was stratified according to CAD, the minor allele of APOD polymorphism was found related to decreased risk for T2DM in the non-CAD group. In logistic regression analysis adjusted for several confounders, LDLR rs5930 polymorphism was found associated with T2DM presence in the male CAD group [OR = 0.502, 95%CI (0.259-0.974), p = 0.042]. Besides, APOD and LIPA polymorphisms were shown to affect serum lipid levels in non-CAD T2DM patients (p < 0.05). The minor allele of APOC1 was found associated with triglyceride levels in males independent of CAD status. Besides, LDLR minor allele carrier females had elevated HbA1c and glucose levels independent from CAD status in the whole group. The cholesterol metabolism-related gene polymorphisms were found associated with T2DM and biochemical parameters stratified to sex, CAD, and T2DM status.


Assuntos
Colesterol/genética , Doença da Artéria Coronariana/genética , Diabetes Mellitus/genética , Idoso , Alelos , Apolipoproteína C-I/genética , Apolipoproteínas D/genética , Colesterol/fisiologia , Doença da Artéria Coronariana/complicações , Diabetes Mellitus/etiologia , Diabetes Mellitus/fisiopatologia , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Genótipo , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Masculino , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores de LDL/genética , Fatores de Risco , Esterol Esterase/genética
7.
Turk Kardiyol Dern Ars ; 48(5): 461-471, 2020 07.
Artigo em Turco | MEDLINE | ID: mdl-32633266

RESUMO

OBJECTIVE: Genetic risk factors that cause coronary artery disease (CAD) demonstrate variations in different populations. In this study, a single nucleotide polymorphism in the APOA5 gene was targeted to determine genetic contributors to atherosclerotic CAD. The effects of this polymorphism on the development of CAD and known risk factors of the disease were examined. METHODS: A total of 448 patients with angina or acute myocardial infarction who underwent coronary angiography were grouped as individuals with normal coronary arteries (≤30% stenosis) and critical disease (≥50% stenosis). The angiographic severity and the extent of atherosclerotic CAD were assessed using the Gensini and SYNTAX scores. Individuals were genotyped for the APOA5-1131T>C polymorphism using hydrolysis probes and the results were evaluated. RESULTS: The APOA5-1131T>C polymorphism was associated with the serum lipid levels in the non-CAD group (p<0.05). In addition, the effect of APOA5 gene polymorphism on clinical status and other parameters was determined to vary depending on gender. A borderline association was found between APOA5 -1131T>C and type 2 diabetes mellitus (p=0.055). This polymorphism was found to be associated with obesity and it was observed that the APOA5 -1131C allele carriers had a reduced risk for obesity (p<0.05). Logistic regression analysis adjusted for age and gender indicated that APOA5 -1131C allele carriage had a protective effect against obesity in the study group (odds ratio: 0.48, 95% confidence interval: 0.29-0.78; p=0.003). CONCLUSION: In this study, the APOA5 gene polymorphism, one of the genetic factors that may lead to atherosclerotic CAD, was found to be associated with obesity. The APOA5 -1131T>C polymorphism was associated with important risk factors for CAD, obesity and serum lipid levels.


Assuntos
Apolipoproteína A-V/genética , Doença da Artéria Coronariana/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Fatores Etários , Alelos , Aterosclerose/sangue , Aterosclerose/genética , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Análise de Regressão , Fatores de Risco , Fatores Sexuais
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