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Amyotrophic lateral sclerosis is a severe neurodegenerative disease whose exact cause is still unclear. Currently, research attention is turning to the mitochondrion as a critical organelle of energy metabolism. Current knowledge is sufficient to confirm the involvement of the mitochondria in the pathophysiology of the disease, since the mitochondria are involved in many processes in the cell; however, the exact mechanism of involvement is still unclear. We used peripheral blood mononuclear cells isolated from whole fresh blood from patients with amyotrophic lateral sclerosis for measurement and matched an age- and sex-matched set of healthy subjects. The group of patients consisted of patients examined and diagnosed at the neurological clinic of the University Hospital Martin. The set of controls consisted of healthy individuals who were actively searched, and controls were selected on the basis of age and sex. The group consisted of 26 patients with sporadic forms of ALS (13 women, 13 men), diagnosed based on the definitive criteria of El Escorial. The average age of patients was 54 years, and the average age of healthy controls was 56 years. We used a high-resolution O2K respirometry method, Oxygraph-2k, to measure mitochondrial respiration. Basal respiration was lower in patients by 29.48%, pyruvate-stimulated respiration (respiratory chain complex I) was lower by 29.26%, and maximal respiratory capacity was lower by 28.15%. The decrease in succinate-stimulated respiration (respiratory chain complex II) was 26.91%. Our data confirm changes in mitochondrial respiration in ALS patients, manifested by the reduced function of complex I and complex II of the respiratory chain. These defects are severe enough to confirm this disease's hypothesized mitochondrial damage. Therefore, research interest in the future should be directed towards a deeper understanding of the involvement of mitochondria and respiratory complexes in the pathophysiology of the disease. This understanding could develop new biomarkers in diagnostics and subsequent therapeutic interventions.
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Elevated levels of D-2-hydroxyglutarate (D-2HG) and L-2-hydroxyglutarate (L-2HG) in the brain are associated with various pathological conditions, potentially contributing to neurological symptoms and neurodegeneration. Previous studies on animal models have revealed their capability to interfere with several cellular processes, including mitochondrial metabolism. Both enantiomers competitively inhibit the enzymatic activity of 2-oxoglutarate-dependent dioxygenases. These enzymes also execute several signaling cascades and regulate the level of covalent modifications on nucleic acids or proteins, e.g., methylation, hydroxylation, or ubiquitination, with an effect on epigenetic regulation of gene expression, protein stability, and intracellular signaling. To investigate the potential impact of 2HG enantiomers on human neuronal cells, we utilized the SH-SY5Y human neuroblastoma cell line as a model. We employed proton nuclear magnetic resonance (1H-NMR) spectroscopy of culture media that provided high-resolution insights into the changes in the content of metabolites. Concurrently, we performed biochemical assays to complement the 1H-NMR findings and to estimate the activities of lactate and 3-hydroxybutyrate dehydrogenases. Our results reveal that both 2HG enantiomers can influence the cellular metabolism of human neuroblastoma cells on multiple levels. Specifically, both enantiomers of 2HG comparably stimulate anaerobic metabolism of glucose and inhibit the uptake of several essential amino acids from the culture media. In this respect, both 2HG enantiomers decreased the catabolism capability of cells to incorporate the leucine-derived carbon atoms into their metabolism and to generate the ketone bodies. These results provide evidence that both enantiomers of 2HG have the potential to influence the metabolic and molecular aspects of human cells. Furthermore, we may propose that increased levels of 2HG enantiomers in the brain parenchyma may alter brain metabolism features, potentially contributing to the etiology of neurological symptoms in patients.
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Glutaratos , Neuroblastoma , Linhagem Celular Tumoral , Sobrevivência Celular , Glutaratos/química , Glutaratos/metabolismo , Hidroxibutirato Desidrogenase/metabolismo , Espectroscopia de Ressonância Magnética , Mitocôndrias/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Estereoisomerismo , HumanosRESUMO
Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH). Blood serum samples from mCRPC patients (n = 51) and BPH patients (n = 48) underwent metabolome analysis through 1H-NMR spectroscopy. The expression levels of serum exosomal miRs in mCRPC and BPH patients were evaluated using a quantitative real-time polymerase chain reaction (qRT-PCR). The 1H-NMR metabolomics analysis revealed significant alterations in lactate, acetate, citrate, 3-hydroxybutyrate, and branched-chain amino acids (BCAAs, including valine, leucine, and isoleucine) in mCRPC patients compared to BPH patients. MiR-15a, miR-16, miR-19a-3p, and miR-21 exhibited a downregulation of more than twofold in the mCRPC group. Significant correlations were predominantly observed between lactate, citrate, acetate, and miR-15a, miR-16, miR-19a-3p, and miR-21. The importance of integrating metabolome analysis of serum with selected serum exosomal miRs in mCRPC patients has been confirmed, suggesting their potential utility for distinguishing of mCRPC from BPH.
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MicroRNAs , Hiperplasia Prostática , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Soro/metabolismo , Citratos , Lactatos , AcetatosRESUMO
STF-083010 is an inhibitor of endonuclease activity of inositol requiring-enzyme 1α (IRE1α) that is involved in activation of IRE1α-XBP1 axis of the unfolded protein response after ER stress. STF-083010 was tested as a possible antitumor agent in some previous studies exhibiting the ability either to induce death of tumour cells or to increase sensitivity of tumours cells to other neoplastic agents. STF-083010 exhibits also hepatoprotective effects in different models of liver injury and hepatic steatohepatitis. We have shown that STF-083010 has significant impact on mitochondrial functions that is not dependent on the way of STF-083010 application. We have observed that STF-083010 decrease of both maximal respiration (representing maximal electron transfer capacity of mitochondrial respiratory chain) and spare respiratory capacity after either incubation of the SH-SY5Y cells with STF-083010 or direct addition of STF-083010 to the respiration medium. In addition, we have documented impact of STF-083010 on generation of mitochondrial membrane potential (ΔΨm) that could be a result of decreased mitochondrial substrate level phosphorylation. Finally, increased sensitivity of ΔΨm to uncoupler in the presence of STF-083010 was documented. Our results indicate that STF-083010 has important impact on mitochondrial functions independently of its ability to inhibit endonuclease activity of IRE1α that is involved in activation of IRE1α-XBP1 axis of the unfolded protein response after ER stress. The impact of STF-083010 on mitochondrial functions could be associated with its possible off-target effect.
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Neuroblastoma , Proteínas Serina-Treonina Quinases , Humanos , Endorribonucleases/metabolismo , Endorribonucleases/farmacologia , Endonucleases/metabolismo , Endonucleases/farmacologia , Potencial da Membrana Mitocondrial , Respiração , Estresse do Retículo Endoplasmático , Proteína 1 de Ligação a X-Box/metabolismoRESUMO
ABSTRACT: Acute myocardial infarction (MI) is the leading cause of mortality worldwide with premenopausal women showing a lower incidence of cardiovascular disease compared with men of the same age. After menopause, this advantage disappears, suggesting that sex hormones play a cardioprotective role. This study was aimed to assess on the activity of antioxidant enzymes in plasma and the respiratory function of isolated heart mitochondria after the induction of MI in rats after ovariectomy and estradiol benzoate supplementation. Sprague-Dawley female rats were ovariectomized 3 months before the induction of MI and supplemented/not supplemented with oestrogen 3 months before/7 days after the induction of MI. No significant differences in glutathione peroxidase activities were found in any group. Differences between values were only significant in the ovariectomized not supplemented group (P < 0.01) for the glutathione reductase activity and glutathione concentrations. In isolated mitochondria (7 days after MI), the decline in respiration was observed comparing the ovariectomized and nonovariectomized group. Respiratory functions did not show significant differences between animals supplemented with oestrogen before MI or treated with oestrogen after MI. Ovariectomy worsened mitochondrial dysfunction after MI, and oestrogen supplementation before or after the induction of MI did not improve mitochondrial function.
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Antioxidantes , Infarto do Miocárdio , Animais , Antioxidantes/farmacologia , Suplementos Nutricionais , Estradiol/farmacologia , Estrogênios , Feminino , Humanos , Mitocôndrias , Infarto do Miocárdio/prevenção & controle , Ovariectomia , Ratos , Ratos Sprague-Dawley , RespiraçãoRESUMO
In the present study we have shown that treatment of SH-SY5Y cells with either thapsigargin or tunicamycin is associated with a significant decrease in ROUTINE and ATP-coupled mitochondrial respiration as well as a decrease in spare and maximal respiratory capacity. We have also shown that treating cells with either thapsigargin or tunicamycin is associated with significant changes in mitochondrial membrane potential (ΔΨm) generation, which is mainly associated with the reversal of the succinyl-CoA ligase reaction and a decreased activity of complex II. Despite the induction of endoplasmic reticulum (ER) specific unfolded protein response (UPR), as documented by increased expression of HRD1, ER stress did not induce mitochondrial UPR since the expression of both mitochondrial protease LONP1 and mitochondrial chaperone HSP60 was not significantly altered. Inhibition of IRE1α ribonuclease with STF-083010 did not protect the SH-SY5Y cells from ER stress-induced mitochondrial dysfunction. STF-083010 itself had significant impact on both mitochondrial respiration and generation of ΔΨm, which has mainly been associated with the uncoupling of respiratory chain from ATP synthesis.
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Estresse do Retículo Endoplasmático , Mitocôndrias/metabolismo , Resposta a Proteínas não Dobradas , Linhagem Celular Tumoral , HumanosRESUMO
The aim of our work was to study effect of antidepressant imipramine on both thapsigargin- and tunicamycin-induced ER stress and mitochondrial dysfunction in neuroblastoma SH-SY5Y cells. ER stress in SH-SY5Y cells was induced by either tunicamycin or thapsigargin in the presence or absence of imipramine. Cell viability was tested by the MTT assay. Splicing of XBP1 mRNA was studied by RT-PCR. Finally, expression of Hrd1 and Hsp60 was determined by Western blot analysis. Our findings provide evidence that at high concentrations imipramine potentiates ER stress-induced death of SH-SY5Y cells. The effect of imipramine on ER stress-induced death of SH-SY5Y cells was stronger in combination of imipramine with thapsigargin. In addition, we have found that treatment of SH-SY5Y cells with imipramine in combination of either thapsigargin or tunicamycin is associated with the alteration of ER stress-induced IRE1α-XBP1 signalling. Despite potentiation of ER stress-induced XBP1 splicing, imipramine suppresses both thapsigargin- and tunicamycin-induced expression of Hrd1. Finally, imipramine in combination with thapsigargin, but not tunicamycin, aggravates ER stress-induced mitochondrial dysfunction without significant impact on intracellular mitochondrial content as indicated by the unaltered expression of Hsp60. Our results indicate the possibility that chronic treatment with imipramine might be associated with a higher risk of development and progression of neurodegenerative disorders, in particular those allied with ER stress and mitochondrial dysfunction like Parkinson's and Alzheimer's disease.
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Estresse do Retículo Endoplasmático/efeitos dos fármacos , Imipramina/farmacologia , Mitocôndrias/efeitos dos fármacos , Neuroblastoma/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Endorribonucleases/metabolismo , Humanos , Neuroblastoma/patologia , Doenças Neurodegenerativas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Splicing de RNA/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tapsigargina/toxicidade , Tunicamicina/toxicidade , Ubiquitina-Proteína Ligases/metabolismo , Proteína 1 de Ligação a X-Box/genéticaRESUMO
The original version of the article is unfortunately missing the Acknowledgements section. Acknowledgments section is given below.
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Mitochondria are organelles with significant cellular functions, especially cellular bioenergetics and apoptosis. They are structural and functional elements of cell respiration with the electron transport system (ETS), whose role is to provide adenosine triphosphate (ATP), used as a source of chemical energy. The Krebs cycle and fatty acid oxidation take place within mitochondria. Other metabolic pathways and cycles include some steps inside and outside the mitochondria (e.g., the urea cycle, steroid biosynthesis, heme biosynthesis, and cardiolipin synthesis). Dysfunction of mitochondria plays a critical role in the pathophysiology of a variety of diseases including degenerative diseases, aging, and cancer, etc. Nowadays the interest of the mitochondrial respiratory function is still increasing due to their importance in the physiology and pathophysiology of an organism. Neuroblastoma cell line SH-SY5Y is widely used as an in vitro model in neurodegenerative diseases, where mitochondrial dysfunction is considered as a key mechanism in pathophysiology of neurodegenerative disorders. This paper gives first insight into the mitochondrial respiration and characterization of SH-SY5Y cells, with basic information of respiration in different coupling control states including ROUTINE, LEAK, and maximal electron transport (ET) capacity.
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Respiração Celular , Metabolismo Energético , Mitocôndrias/fisiologia , Neuroblastoma/metabolismo , Trifosfato de Adenosina/biossíntese , Linhagem Celular Tumoral , Humanos , Neuroblastoma/patologia , OxirreduçãoRESUMO
INTRODUCTION: The genetic background of bronchial asthma is complex, and it is likely that multiple genes contribute to its development both directly and through gene-gene interactions. Cytokines contribute to different aspects of asthma, as they determine the type, severity and outcomes of asthma pathogenesis. Allergic asthmatics undergoing an asthmatic attack exhibit significantly higher levels of pro-inflammatory cytokines, such as interleukins and chemokines. In recent years, cytokines and their receptors have been shown to be highly polymorphic, and this prompted us to investigate interleukin 6 promoter polymorphisms at position -174G/C (rs1800795) and at -572G/C (rs1800796) in relation to asthma in children. METHODS: Interleukin 6 promoter polymorphisms were analyzed in bronchial asthma patients and healthy children using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: We observed a significant association between polymorphism at -174G/C and bronchial asthma (OR=3.4, 95% CI: 2.045-5.638, P<.001). Higher associations between polymorphism at IL-6 -174G/C and bronchial asthma were observed in atopic patients (OR=4.1, 95% CI: 2.308-7.280, P<8.10-7). CONCLUSIONS: Interleukin 6 polymorphism is associated with bronchial asthma, particularly its atopic phenotype. Expression and secretion of interleukins in asthmatic patients may be affected by genetic polymorphisms, and could have a disease-modifying effect in the asthmatic airway and modify the therapeutic response.
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Asma/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Alelos , Asma/epidemiologia , Criança , Pré-Escolar , Comorbidade , Feminino , Frequência do Gene , Genótipo , Humanos , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/genética , Lactente , Testes Intradérmicos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Regiões Promotoras Genéticas/genética , Eslováquia/epidemiologia , EspirometriaRESUMO
BACKGROUND: Major depressive disorder (MDD) is a main public health concern worldwide. Despite extensive investigations, the exact mechanisms responsible for MDD have not been identified. Epidermal growth factor (EGF) and insulin growth factor binding protein-3 (IGFBP-3) are involved in brain function. Tumour suppressor protein p53 is widely involved in neuronal death in response to different forms of acute insults and neurological disorders. The present study focuses on the possible associations of the single-nucleotide polymorphisms (SNP) of EGF A61G (rs4444903), IGFBP-3 C32G (rs2854746) and TP53 G72C (rs1042522) genes with MDD risk in the Slovak population. METHODS: The present case-control association study was carried out in 111 confirmed MDD patients and 207 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: Logistic regression analysis showed no association between SNPs of selected genes and MDD risk in the Slovak population. However, the stratification of individuals by gender revealed that males carrying IGFBP-3 G alleles (G32G or GG) had marginally increased risk for developing MDD as compared to CC homozygous males (p=0.09). In women, inverse association was observed between SNP rs1042522 and MDD risk (p=0.04 for recessive model). CONCLUSION: Our results suggest the protective effect of minor allele 72C of TP53 gene towards MDD. The disruption of mechanisms involved in cell survival and death regulation may be involved in pathophysiology of MDD.
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Transtorno Depressivo Maior/genética , Fator de Crescimento Epidérmico/genética , Genes p53/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Eslováquia/epidemiologiaRESUMO
OBJECTIVES: Bronchial asthma is a chronic respiratory disease characterized by airway inflammation. There is increasing evidence that neurotrophins play an important role in the development and maintenance of neurogenic airway inflammation in chronic allergic diseases. WORKING HYPOTHESIS: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and has several important functions in the airways. There are only a few reports on the association between genetic variations in the BDNF gene and various allergic diseases, and the results are generally conflicting. Therefore, we aimed to study the functional polymorphism Val66Met (also called rs6265 or G196A) in the BDNF gene in a group of asthmatic children and healthy controls. STUDY DESIGN, PATIENT-SELECTION, AND METHODOLOGY: We studied 248 asthmatic patients (aged 12.28 ± 0.24 years) and 249 healthy children (aged 13.14 ± 0.48 years). Analysis of the Val66Met polymorphism of the BDNF gene was performed by polymerase chain reaction (PCR) and PCR products were digested by PmlI. RESULTS: The prevalence of the Val66Met polymorphisms (Val/Val, Val/Met, and Met/Met) was 61.7%, 33.5%, and 4.8% in asthmatics, respectively, and 47.0%, 51.8%, and 1.2% in healthy subjects, respectively. We observed a significant association of the Met/Met variant genotype with asthmatics (OR = 4.17, 95% CI = 1.16-14.96, P = 0.018). The Val/Met genotype was protective against bronchial asthma (OR = 0.69, 95% CI = 0.48-0.99, P = 0.045), especially in girls (OR = 0.34, 95% CI = 0.20-0.59, P = 0.001). CONCLUSION: Specific BDNF gene polymorphism may contribute to bronchial asthma susceptibility. Our study suggested the positive association between selected functional BDNF polymorphism (rs6265) and asthma in children.
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Asma/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Polimorfismo Genético , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , MasculinoRESUMO
Tumors of brain tissue and meninges create a heterogeneous group with various biological behavior, therapy management and differing prognosis. Some of these do not require treatment, some can be cured by surgery and some are rapidly fatal despite treatment. Despite huge progress in tumor research, innovations in diagnostic tools and therapy, prognosis remains, in case of malignant tumor types, very serious. There has been an increased understanding of molecular abnormalities occurring in primary brain tumors. Genome-wide analyses of tumors have improved the knowledge in tumor biology. The aim of the research is to explain the oncogenesis features thus leading to the use of new therapeutic modalities in order to prolong survival rate of patients and at the same time providing satisfactory life quality. This article offers a short review of the basic genetic alterations present with some histological types of brain tumors.
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Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Astrocitoma/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/genética , Ependimoma/metabolismo , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Glioma/metabolismo , Humanos , Imuno-Histoquímica , Linfoma/metabolismo , Meduloblastoma/metabolismo , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Oligodendroglioma/metabolismo , PrognósticoRESUMO
INTRODUCTION: Bronchial asthma is a complex disease in which genetic factors, environmental factors and oxidative damage are responsible for the initiation and modulation of disease progression. If antioxidant mechanisms fail, reactive oxygen species damage the biomolecules followed by progression of the disease. Catalase is one of the most important endogenous enzymatic antioxidants. In the present study, we examined the hypothesis that increased oxidative damage and polymorphism in the CAT gene (-262 promoter region, C/T) are associated with childhood bronchial asthma. PATIENTS AND METHODS: Genotyping of the polymorphisms in the CAT gene in healthy (249) and asthmatic children (248) was performed using polymerase chain reaction-restriction fragment length polymorphism. Markers of oxidative damage: content of sulfhydryl groups and thiobarbituric acid-reactive substances were determined by spectrophotometry in children. RESULTS: The TT genotype of catalase was more frequent among the asthmatic patients (22.6%) than in healthy children (4.8%) (odds ratio=5.63; 95% confidence interval=2.93-10.81, P<.001). The amount of sulfhydryl groups decreased significantly and conversely, the content of thiobarbituric acid-reactive substances increased significantly in bronchial asthma and in catalase TT genotype compared to other catalase genotypes of this gene. CONCLUSIONS: These results suggest that catalase polymorphism might participate in development of bronchial asthma and in enhanced oxidative damage in asthmatic children. Genetic variation of enzymatic antioxidants may modulate disease risk.
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Asma/genética , Catalase/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Adolescente , Asma/epidemiologia , Asma/metabolismo , Proteínas Sanguíneas/química , Testes Respiratórios , Criança , Feminino , Volume Expiratório Forçado , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Peroxidação de Lipídeos/genética , Masculino , Estresse Oxidativo/genética , Pico do Fluxo Expiratório , Eslováquia/epidemiologia , Compostos de Sulfidrila/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
The aim of our study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, PvuII and XbaI, on the development of prostate cancer within Slovak population, as well as their correlation with selected clinical characteristics. The study was performed using 311 prostate cancer patients and 256 healthy male controls. Both polymorphisms were significantly associated with higher risk of prostate cancer development. At the same time, the CC genotype of PvuII polymorphism (OR = 1.98; 95% CI 0.94-4.21; p = 0.05) and the AG genotype of XbaI polymorphism (OR = 1.74; 95% CI 1.0-3.02; p = 0.04) significantly contributed to the development of low-grade carcinoma, while the AG and GG genotypes of the XbaI polymorphism contributed mainly to the development of high-grade prostate cancer (OR = 1.83; 95% CI 1.12-3.01; p = 0.01 and OR = 2.13; 95% CI 1.06-4.19; p = 0.03, respectively). Similarly, the AG and GG genotypes of XbaI polymorphism showed significant association with prostate cancer in patients with serum PSA level ≥10 ng/ml. Both polymorphisms were found at the same time to be more frequent in patients diagnosed before the age of 60. We conclude on the basis of these results that PvuII and XbaI polymorphisms of estrogen receptor alpha might be associated with prostate cancer risk within Slovak population. Although this is a pilot study and, as such, more detailed investigations are needed to confirm the role of these polymorphisms in prostate cancer development and progression within said Slovak population, our results might still provide a valuable basis for further research with larger patient groups.
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Receptor alfa de Estrogênio/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo Genético , Neoplasias da Próstata/genética , Idoso , Alelos , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Fatores de Risco , EslováquiaRESUMO
Major depressive disorder (MDD) is a complex neuropsychiatric disorder where both gene-gene and gene-environment interactions play an important role, but the clues are still not fully understood. One carbon metabolism in the CNS plays a critical role in the synthesis and release of neurotransmitters which are relevant to depressive disorder. We studied genetic polymorphisms of the brain derived neurotrophic factor (BDNF) and the methylenetetrahydrofolate reductase (MTHFR) in association with major depressive disorder. We genotyped the BDNF G196A, the MTHFR C677T, and A1298C polymorphisms in 134 patients diagnosed with major depression and 143 control subjects in Slovak (Caucasian) cohort of patients and probands. We found no significant association of either the BDNF G196A or MTHFR C677T polymorphisms with major depressive disorder neither in female nor male group of patients. However, the MTHFR A1298C genotype distribution was 36.6% (for AA genotype), 48.5% (AC) and 14.9% (CC) for the depressed patients, and 48.9% (AA), 42.7% (AC) and 8.4% (CC), respectively, for the control subjects. Patients with MDD had a higher prevalence of the CC genotype (OR = 2.38; 95% CI = 1.07-5.32; p = 0.032) and the AC + CC genotype (OR = 1.67; 95% CI = 1.03-2.69; p = 0.037) in comparison with the control subjects. This study shows that CC genotype of the MTHFR A1298C is associated with higher risk of MDD in Slovak population.