Andrea Evinova

Frecuencia del polimorfismo -262 C/T en el gen de la catalasa y lesión oxidativa en niños eslovacos con asma bronquial

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.

Analysis of genetic polymorphisms of brain-derived neurotrophic factor and methylenetetrahydrofolate reductase in depressed patients in a Slovak (Caucasian) population.

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.

Val66Met polymorphism in the BDNF gene in children with bronchial asthma

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.

Most frequent molecular and immunohistochemical markers present in selected types of brain tumors

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.

Oxidative Damage and Bronchial Asthma

All organisms live in the environment that contains oxygen which is vital for all aerobic organisms, and reactive oxygen species (ROS) which are formed in cells as a consequence of aerobic metabolism. Moreover mitochondrial respiration (a base of energetic production in all eukaryotic organisms) is associated with an inevitable electron leak, resulting in a nonstop production of reactive oxygen species, such as superoxide anion radical, hydrogen peroxide and hydrogen radical. Universal nature of reactive oxygen species is underlined by the presence of one enzyme superoxide dismutase. This enzyme occurs in all aerobic organisms and it is responsible for dismutation of superoxide anions into oxygen and hydrogen peroxide. Genes involved in detoxification of reactive oxygen species are highly conserved among eukaryotes and their deficiency could be limit of several diseases and life span. Oxidative stress is a unique pathophysiological condition resulting from the disrupted balance between oxidants and antioxidants. Increased level of reactive oxygen species may cause oxidative damage of all biomolecules: nucleic acids, proteins, lipids, saccharides. A progressive grow of oxidative damage is the result of increasing production of reactive oxygen species or an insufficient antioxidant defence system and this damage may contribute to the origin and development of several diseases including bronchial asthma, but on the other hand oxidative damage can be the consequence of them as well (fig. 1).

Alzheimer's Disease: Definition, Molecular and Genetic Factors

Frequency of neurodegenerative diseases increase significantly with the age. One of the most frightening and devastating of all neurological disorders is the dementia that occurs in the elderly. Dementia is a common name for progressive degenerative brain syndromes which affect memory, thinking, behaviour and emotions. Dementia mainly affects older people, although there is a growing incidence of the cases that start before the age of 65. After age 65, the likelihood of developing dementia roughly doubles every five years. Dementia affects 1 – 6% of human population over 65 years and 10 – 20% over 80 years. In the present, average age is increasing and the number of people over 60 years increases as well. Although Ageing is a physiological process, however it seems to be linked with an increasing risk of origin and development of several diseases including neurodegenerative disorders. Dementia is characterised by the loss of or decline in memory and other cognitive abilities. It is caused by various diseases and conditions resulting in damaging brain cells. Different types of dementia (Alzheimer`s disease, vascular dementia or post-stroke dementia, mixed dementia, dementia with Lewy bodies, Parkinson`s disease, frontotemporal dementia, Creutzfeld-Jacob disease, normal pressure hydrocephalus) have been associated with distinct symptom patterns and distinguishing microscopic brain abnormalities. Alzheimers disease (AD) is the most common cause of dementia and this disease represents 60 – 80% of all dementia. Alzheimers disease is age-related disease and it is characterized by a range of changes in brain anatomy, biochemistry, genetic, and function. According to Alzheimer`s disease International in 2010, there were an estimated 35.6 million people with dementia worldwide. This means a 10 percent increase over previous global dementia prevalence reported in 2005 in The Lancet. Number of people with dementia will be increasing to 65.7 million by 2030 and 115.4 million by 2050. Hallmark abnormalities of Alzheimer`s disease are deposits of the protein fragment ┚-amyloid (plaques) and twisted strands of the protein tau (tangles). Protein oxidation and generation of protein aggregates may be caused by loss of cell function alike a decreased ability of old organisms to resist the physiological stresses and oxidative damage. The relationship between protein aggregation, oxidative damage and neurodegenerative

Asociación entre polimorfismos genéticos de la interleucina 6 y el asma bronquial en niños

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.

Oxidative Changes and Possible Effects of Polymorphism of Antioxidant Enzymes in Neurodegenerative Disease

Frequency of neurodegenerative diseases increase significantly with the age. In the present, average age is increasing and the number of people over 60 years increases as well. Ageing is a physiological process; however it seems to be linked with an increasing risk of origin and development of several diseases including neurodegenerative disorders such as Alzheimers disease, Parkinson’s disease, and Huntington’s disease. Exact mechanisms of ageing are still unclear but experimental evidences support a hypothesis that ageing changes are consequen‐ ces of increasing oxidative damage of organs, tissues, cells and all biomolecules. Oxidative damage is elevated when production of reactive oxygen species is increased compared to the physiological condition or a defence ability of organism against attacks of reactive oxygen species is decreased. Oxidation of specific proteins could play a key role in age associated damage. A relationship between protein aggregation, oxidative stress and neurodegeneration remains unclear although neurodegenerative diseases are connected with an origin of protein deposits. It assumes that protein oxidation and generation of protein aggregates generate a base for a loss of cell function and a reduced ability aged organisms to resist to physiological stress. Accumulation of modified proteins, disturbance of ion homeostasis, lipid and DNA modifications, and impairment of energy production are some of the crucial mechanisms linking ageing to neurodegeneration. In addition mitochondrial dysfunction plays a key role in neurology. Damage of mitochondrial electron transport may be an important factor in the pathogenesis of neurodegenerative diseases, such as Alzheimers, Parkinsons, and Hunting‐ tons diseases.

Association of EGF, IGFBP-3 and TP53 Gene Polymorphisms with Major Depressive Disorder in Slovak Population

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.