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ABSTRACT: Spermatozoa have a highly complex RNA profile. Several of these transcripts are suggested as biomarkers for male infertility and contribute to early development. To analyze the differences between sperm RNA quantity and expression of protamine (PRM1 and PRM2) and testis-specific histone 2B (TH2B) genes, spermatozoa from 33 patients who enrolled in assisted reproduction treatment (ART) program were analyzed. Sperm RNA of teratozoospermic (T), oligoteratozoospermic (OT), and normozoospermic (N) samples was extracted, and the differences in transcript levels among the study groups were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The correlations of total RNA per spermatozoon and the expression of the transcripts were evaluated in relation to sperm characteristics and preimplantation embryo development. The mean (±standard deviation) RNA amount per spermatozoon was 28.48 (±23.03) femtogram in the overall group and was significantly higher in the OT group than that in N and T groups. Total sperm RNA and gene expression of PRM1 and PRM2 genes were related to preimplantation embryo development and developmental arrest. Specific sperm characteristics were correlated with the expressions of PRM1, PRM2, or TH2B genes. We conclude that the sperm RNA amount and composition are important factors and might influence early embryonic development and also differ in different cases of male infertility.
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BACKGROUND AND AIM: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality globally despite advancements in treatment. Long non-coding RNAs (lncRNAs) play crucial roles in the atherosclerotic process, with ANRIL being one such lncRNA. This study explored the association between ANRIL polymorphisms (rs1333049:C > G, rs564398:T > C, and rs10757274:A > G) and CAD along with CAD risk factors in a Turkish patient group. METHODS: The study included 1285 participants, consisting of 736 patients diagnosed with CAD (mean age = 63.3 ± 10.5 years) and 549 non-CAD controls (mean age = 57.52 ± 11.01 years). Genotypes for rs1333049, rs564398, and rs10757274 were determined using qRT-PCR. RESULTS: G allele carriage of both rs1333049 and rs10757274 polymorphisms were associated with higher Gensini score, SYNTAX score, total cholesterol, and triglyceride levels in female CAD patients and non-CAD males. Females with rs564398 CC genotype were more susceptible to CAD (p = 0.02) and severe CAD (p = 0.05). Moreover, the G and T alleles of rs10757274 and rs564398 were more prevalent among hypertensive males. Also, carrying the C allele for rs564398 was associated with a decreased risk for type 2 diabetes mellitus (T2DM) (p = 0.02). Besides, carriers of the rs1333049 C allele for decreased risk for T2DM (p = 0.03) and CAD complexed with T2DM (p = 0.04) in logistic regression analyses. CONCLUSIONS: In conclusion, selected ANRIL polymorphisms were associated with CAD presence/severity and CAD risk factors, T2DM, and hypertension. Notably, this study, the largest sample-sized study examining the effects of selected polymorphisms on CAD and its risk factors among Turkish individuals, supported the findings of previous studies conducted on different ethnicities.
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Doença da Artéria Coronariana , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , Estudos de Casos e Controles , Doença da Artéria Coronariana/genética , Genótipo , Fatores de Risco , RNA Longo não Codificante/genética , Turquia/epidemiologiaRESUMO
BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide despite advanced treatment and diagnosis strategies. Angiopoietin-like protein 8 (ANGPTL8) mainly functions in the lipid mechanism, which is a dysregulated mechanism during CAD pathogenesis. In this study, we aimed to determine the associations between an ANGPTL8 polymorphism rs2278426 and the severity, presence, and risk factors of CAD. METHODS: A total of 1367 unrelated Turkish individuals who underwent coronary angiography were recruited for the study and grouped as CAD (n = 736, ≥50 stenosis) and non-CAD (n = 549, ≤30 stenosis). Also, subjects were further divided into groups regarding type 2 diabetes mellitus (T2DM) status. Subjects were genotyped for rs2278426 (C/T) by quantitative real-time PCR. Secondary structure analyses of protein interactions were revealed using I-TASSER and PyMOL. RESULTS: Among CAD patients, T allele carriage frequency was lower in the T2DM group (p = 0.046). Moreover, in male non-CAD group, T allele carriage was more prevalent among T2DM patients than non-T2DM (p = 0.033). In logistic regression analysis adjusted for obesity, T allele carrier males had an increased risk for T2DM in non-CAD group (OR = 2.244, 95 % CI: 1.057-4.761, p = 0.035). Also, in T2DM group, stenosis (p = 0.002) and SYNTAX score (p = 0.040) were lower in T allele carrier males than in non-carriers. Analyzes of secondary structure showed that ANGPTL8 could not directly form complexes with ANGPTL3 or ANGPTL4. CONCLUSION: In conclusion, T allele carriage of ANGPTL8 rs2278426 has a protective effect on CAD in T2DM patients. Further research should be conducted to explore the association between ANGPTL8 polymorphism (rs2778426) and CAD.
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Alelos , Proteína 8 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Feminino , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Pessoa de Meia-Idade , Doença da Artéria Coronariana/genética , Proteínas Semelhantes a Angiopoietina/genética , Idoso , Hormônios Peptídicos/genética , Predisposição Genética para Doença , Turquia , Angiografia Coronária , Frequência do Gene , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: Epicardial adipose tissue (EAT) surrounds the heart and coronary arteries and is important for comprehending the pathogenesis of coronary artery disease (CAD). We aimed to evaluate the expressions of mitochondrial biogenesis- and CAD-related genes and miRNAs in EAT by comparing them to visceral adipose tissue (VAT) in CAD, diabetes, and obesity subgroups. METHODS: In this study, a total of 93 individuals were recruited, and EAT samples (63 CAD; 30 non-CAD) and VAT samples from 65 individuals (46 CAD; 19 non-CAD) were collected. For further analysis, the study population was divided according to obesity and diabetes status. PRKAA1, PPARGC1A, SIRT1, RELA, TNFA, and miR-155-5p, let-7g-5p, miR-1247-5p, miR-326 expression levels were examined. RESULTS: PRKAA1 and let-7g-5p were differentially expressed in EAT compared to VAT. TNFA expression was upregulated significantly in both tissues of CAD patients. In EAT, PRKAA1, PPARGC1A, and SIRT1 were downregulated with diabetes. Moreover, PPARGC1A expression is decreased under the condition of obesity in both tissues. EAT expressions of miR-1247-5p and miR-326 were downregulated with obesity, while miR-155-5p is decreased only in the VAT of obese. Also, miRNAs and genes were correlated with biochemical parameters and each other in EAT and VAT (p < 0.050). CONCLUSIONS: The findings demonstrating distinct let-7g-5p and AMPKα1 mRNA expression between EAT and VAT underscores the importance of tissue-specific regulation in different clinical outcomes. In addition, the differential expressions of investigated genes and miRNAs highlight their responsiveness to obesity, DM, and CAD in adipose tissues.
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Doença da Artéria Coronariana , Diabetes Mellitus , MicroRNAs , Humanos , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Tecido Adiposo Epicárdico , Biogênese de Organelas , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Diabetes Mellitus/metabolismoRESUMO
BACKGROUND: Increasing mortality and morbidity of coronary artery disease (CAD) highlight the emerging need for novel noninvasive markers such as circulating microRNAs (miRNAs). OBJECTIVE: To evaluate the circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326, and their associations with known contributors to CAD, in CAD subgroups. METHODS: We divided the cohort into 4 groups: non-CAD controls (≤30% stenosis; n = 55), and patients with stable angina pectoris (SAP; n = 48), unstable AP (UAP; n = 46), and myocardial infarction (MI; n = 36). The circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326 were determined using TaqMan Advanced miRNA Assays in serum specimens. RESULTS: Circulating miR-126-3p levels were lower in the MI and UAP groups, compared with the non-CAD group, whereas miR-210-3p circulating levels were lower in the MI group than others. The levels of circulating let-7g-5p were shown to be useful for distinguishing UAP from MI, and there were substantial differences in circulating let-7g-5p levels between the UAP and MI groups. Moreover, lipid levels and ratios were lower in individuals with high circulating miR-126-3p and miR-210-3p levels. CONCLUSIONS: The study results suggest that circulating miR-126-3p, miR-210-3p, and let-7g-5p are differentiated between different clinical presentations of CAD and associated with lipid levels, which are important risk factors and determinants of CAD.
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BACKGROUND: MicroRNAs have been found to have an essential role in cardiovascular diseases. In previous experiments, the changed expressions of miR-26a-5p and miR-19a-3p were confirmed in patients with severe coronary atherosclerosis by miRNA microarrays. However, the role of two miRNAs in coronary artery diseases (CAD) still needs to be investigated further. Our current study aimed to analyse two miRNAs in angiographically confirmed CAD and non-CAD with insignificant coronary stenosis. This study aimed to identify the potential diagnostic value of circulating miRNA with CAD. METHODS: The CAD patients (n = 50) and non-CAD controls (n = 43) were studied. miRNAs (miR-26a-5p and miR-19a-3p) were quantified by TaqMan miRNA assays using real-time PCR. We subsequently assessed the diagnostic value of the miRNAs and correlations of miRNA with clinical parameters. Target prediction tools were utilised to identify miRNA target genes. RESULTS: The expression of miR-26a-5p was significantly increased in CAD compared to non-CAD controls (p < 0.05). Tertile groups were formed according to the expression levels of miRNAs, and high expression tertile (T3) was compared with low expression tertile (T1). It was found that CAD presence was more prevalent in T3 of miR-26a-5p, and the frequency of diabetes was higher in T3 of miR-19a-3p. There were significant correlations between miRNAs and diabetes risk factors such as HbA1c, glucose levels, and BMI (p < 0.05). CONCLUSIONS: Our findings show that miR-26a-5p expression is altered in CAD presence while miR-19a-3p expression is different in diabetes. Both miRNAs are closely related to risk factors of CAD, therefore, could be therapeutic targets for CAD treatment.
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MicroRNA Circulante , Doença da Artéria Coronariana , Estenose Coronária , MicroRNAs , Humanos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/genética , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNA Circulante/genética , Fatores de Risco , BiomarcadoresRESUMO
The anti-inflammatory adipokine intelectin-1, which is encoded by the ITLN1 gene, is hypothesized to be linked to the pathogenesis of type 2 diabetes (T2DM) and obesity. The purpose of this study was to examine the effect of the ITLN1 gene polymorphism rs2274907 on obesity and T2DM in Turkish adults. The impact of genotype on lipid profiles and serum intelectin levels in the obese and diabetes groups was also investigated. Randomly selected 2266 adults (mean age, 55.0 ± 11.7 years; 51.2% women) participating in the population-based Turkish adult risk factor study were cross-sectionally analyzed. The genotyping of rs2274907 A > T polymorphism was performed by using the hybridization probe based LightSNiP assay in real-time PCR. T2DM were defined using the criteria of the American Diabetes Association. Obesity was described as Body mass index ≥ 30 kg/m2. Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements. According to findings, there was no vital connection between the rs2274907 polymorphism and obesity, T2DM, or serum intelectin-1 level. The TA+AA carriers had significantly higher triglyceride levels (p = 0.007) compared with the TT carriers in both obese and T2DM women when adjusted for relevant covariates. ITLN1 rs2274907 polymorphism is not correlated with the risk of obesity and T2DM and not affect serum ITLN1 levels in Turkish adults. However, this polymorphism appears to be important in regulating triglyceride levels in obese and diabetic women.
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Diabetes Mellitus Tipo 2 , Lectinas , Obesidade , Humanos , Obesidade/genética , Diabetes Mellitus Tipo 2/genética , Lipídeos/sangue , Lectinas/sangue , Lectinas/genética , Citocinas/sangue , Citocinas/genética , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/genética , Fatores de Risco , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Genótipo , Frequência do GeneRESUMO
Mitochondria are cell organelles that play an important role in various cellular processes, especially in aerobic respiration and energy production. Although it has its own genome, the mitochondrial genome does not encode all of the proteins necessary for the mitochondria to function. Nuclear genome is needed for increased mitochondrial number, metabolic activities associated with mitochondria, and replication of mitochondrial deoxyribonucleic acid. As a result of mitochondria dysfunction in cells, oxidative stress occurs with the formation of reactive oxygen species, a product of oxidative metabolism, and the oxidant/antioxidant imbalance. Reactive oxygen species damage cellular molecules such as proteins, ribonucleic acid, deoxyribonucleic acid, and mitochondrial deoxyribonucleic acid under the conditions of oxidative stress. Molecular changes as a result of the reactive oxygen species cause the loss of mitochondria function, resulting in an increased number of dysfunctional mitochondria. Thus, the loss of function of mitochondria and defects in oxidative metabolism increase the formation of reactive oxygen species and cause an increase in mutations in mitochondrial deoxyribonucleic acid. These results also aï¬ect mitochondrial biogenesis and accelerate the formation of multifactorial diseases as a result of the decrease in the number of functional mitochondria. In addition, microribonucleic acids, one of the epigenetic regulators, regulate nuclear and mitochondrial genes that control mitochondrial functions. Mitochondrial deoxyribonucleic acid mutated with reactive oxygen species, altered nuclear genome regulators and micro-ribonucleic acids, have been associated with various diseases mediated by mitochondrial dysfunction, including aging and coronary artery disease.
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Doença da Artéria Coronariana , Humanos , Espécies Reativas de Oxigênio/metabolismo , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Estresse Oxidativo/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismoRESUMO
Organelles whose functions change as a result of molecular processes are involved in the pathogenesis of atherosclerosis, which is the main cause of coronary artery disease, in addition to molecular processes. Recently, the role of mitochondria in the pathogenesis of coronary artery disease has attracted the attention of researchers. Mitochondria is a cell organelle with its own genome that plays a regulatory role in aerobic respiration, energy production, and cell metabolism. The number of mitochondria in cells changes dynamically, and there are di���erent numbers of mitochondria in every tissue and every cell, depending on their function and energy needs. Oxidative stress causes mitochondrial dysfunction by leading to alterations in the mitochondrial genome and mitochondrial biogenesis. The dysfunctional mitochondria population in the cardiovascular system is closely related to the coronary artery disease process and cell death mechanisms. It is thought that the altered mitochondria (dys)function accompanying the molecular changes in the atherosclerosis process will be among the new therapeutic targets of coronary artery disease in the near future.
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Aterosclerose , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/fisiologiaRESUMO
BACKGROUND: Pathogenic missense variants in PRKAG2, the gene for the gamma 2 regulatory subunit of adenosine monophosphate-activated protein kinase (AMPK), cause severe progressive cardiac disease and sudden cardiac death, named PRKAG2 cardiomyopathy. In our previous study, we reported a E506K variant in the PRKAG2 gene that was associated with this disease. This study aimed to functionally characterize the three missense variants (E506K, E506Q, and R531G) of PRKAG2 and determine the possible effects on AMPK activity. METHODS: The proband was clinically monitored for eight years. To investigate the functional effects of three missense variants of PRKAG2, in vitro mutagenesis experiments using HEK293 cells with wild and mutant transcripts and proteins were comparatively analyzed using quantitative RT-PCR, immunofluorescence staining, and enzyme-linked immunosorbent assay. RESULTS: In the long-term follow-up, the proband was deceased due to progressive heart failure. In the in vitro experimental studies, PRKAG2 was overexpressed after 48 h of transfection in three mutated cells, after which the expression levels of PRKAG2 were regressed to the level of wild-type cells in 3-weeks stably transformed cells, except for the cells with E506K variant. E506K, E506Q, and R531G variants had caused a reduction in the AMPK activity and resulted in the formation of cytoplasmic glycogen deposits. CONCLUSION: Three missense variants that alter AMPK activity affect a residue in the CBS4 domain associated with ATP/AMP-binding. Detailed information on the influence of PRKAG2 pathogenic variants on AMPK activity would be helpful to improve the treatment and management of patients with metabolic cardiomyopathy.
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Proteínas Quinases Ativadas por AMP , Cardiomiopatias , Mutação de Sentido Incorreto , Proteínas Quinases Ativadas por AMP/metabolismo , Cardiomiopatias/genética , Glicogênio/metabolismo , Células HEK293 , Humanos , Mutação , Fatores de Transcrição/genéticaRESUMO
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.
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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 RiscoRESUMO
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.
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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 RiscoRESUMO
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.
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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 RiscoRESUMO
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.
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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 ÚnicoRESUMO
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.
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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 , TurquiaRESUMO
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.
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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/genéticaRESUMO
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 SexuaisRESUMO
Polymorphisms in the ESR1 gene have been associated with obesity and lipid metabolism. There are also important sex-related differences in the prevalence of obesity and related phenotypes. Therefore, we aimed to interrogate the association of the ESR1 rs2175898 gene polymorphism with obesity, obesity-related variables, and lipid levels in men and women as separate groups. Two thousand twenty-two randomly selected middle-aged and elderly Turks were genotyped for ESR1 rs2175898 polymorphism using real-time polymerase chain reaction with hybridization probes. We found sex-related differences of the ESR1 rs2175898 polymorphism in obesity. Logistic regression analysis after adjustment for age, smoking status, physical activity, diabetes mellitus, and the presence of menopause status in women demonstrated significantly decreased risk for obesity in female AG genotype carriers (OR 0.69; 95% CI 0.52-0.91; p = 0.010), and in male GG genotype carriers (OR 0.49; 95% CI 0.25-0.96; p = 0.039), Furthermore, carriers of the rs2175898 G allele exhibited a lower body mass index in both sexes and decreased waist circumference in women but not in men. Our findings also showed significantly higher serum total-C levels (p = 0.007) in the carriers of the AG+GG/AG genotype compared with the AA genotype in men. The AG genotype of the ESR1 rs2175898 polymorphism in women and GG genotype in men were found to have a decreased likelihood for obesity compared with the other rs2175898 genotypes.
Assuntos
Alelos , Receptor alfa de Estrogênio/genética , Obesidade/genética , Polimorfismo Genético , Caracteres Sexuais , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Coronary artery disease (CAD) is still the preliminary cause of mortality and morbidity in the developed world. Identification of novel predictive and therapeutic biomarkers is crucial for accurate diagnosis, prognosis and treatment of the CAD. The aim of this study was to detect novel candidate miRNA biomarker that may be used in the management of CAD. We performed miRNA profiling in whole blood samples of angiographically confirmed Turkish men with CAD and non-CAD controls with insignificant coronary stenosis. Validation of microarray results was performed by qRT-PCR in a larger cohort of 62 samples. We subsequently assessed the diagnostic value of the miRNA and correlations of miRNA with clinical parameters. miRNA-target identification and network analyses were conducted by Ingenuity Pathway Analysis (IPA) software. Hsa-miR-584-5p was one of the top significantly dysregulated miRNA observed in miRNA microarray. Men-specific down-regulation (p = 0.040) of hsa-miR-584-5p was confirmed by qRT-PCR. ROC curve analysis highlighted the potential diagnostic value of hsa-miR-584-5p with a power area under the curve (AUC) of 0.714 and 0.643 in men and in total sample, respectively. The expression levels of hsa-miR-584-5p showed inverse correlation with stenosis and Gensini scores. IPA revealed CDH13 as the only CAD related predicted target for the miRNA with biological evidence of its involvement in CAD. This study suggests that hsa-miR-584-5p, known to be tumor suppressor miRNA, as a candidate biomarker for CAD and highlighted its putative role in the CAD pathogenesis. The validation of results in larger samples incorporating functional studies warrant further research.