RESUMO
OBJECTIVE: The objective of the study was to evaluate the neurocognitive profile and its relation with Ala16ValMnSOD polymorphism in epilepsy and if these clinical parameters are linked to oxidative stress and inflammatory markers. METHODS: Patients with epilepsy (nâ¯=â¯31) and healthy subjects (nâ¯=â¯42) were recruited. A neuropsychological evaluation was performed in both groups through a battery of cognitive tests. Oxidative stress, inflammatory markers, apoptotic factors, and deoxyribonucleic acid (DNA) damage were measured in blood samples. RESULTS: Statistical analyses showed the association of MnSOD Ala16Val polymorphism with cognitive impairment, including praxis, perception, attention, language, executive functions, long-term semantic memory, short-term visual memory, and total memory in patients with epilepsy and Valine-Valine (VV) genotype compared with the control group. Compared with the controls and patients with epilepsy, Alanine-Alanine (AA), and Alanine-Valine (AV) genotype, the patients with epilepsy and VV genotype exhibited higher levels of tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), activation of caspases 1 and 3 (CASP-1 and -3), and DNA damage. Our findings also showed higher carbonyl protein and thiobarbituric acid reactive substances (TBARS) levels as well as an increased superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities in patients with epilepsy and VV genotype. CONCLUSION: This study supports the evidence of a distinct neuropsychological profile in patients with epilepsy, especially those with the VV genotype. Furthermore, our results suggest that oxidative and inflammatory pathways may be associated with genetic polymorphism and cognitive dysfunction in patients with epilepsy.
Assuntos
Disfunção Cognitiva , Epilepsia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/genética , Epilepsia/complicações , Epilepsia/genética , Genótipo , Humanos , Estresse Oxidativo/genética , Polimorfismo Genético , Superóxido Dismutase/genéticaRESUMO
The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to inflammatory pathways and many metabolic disorders, such as obesity and dyslipidemia. Metabolic syndrome (MetS) is an emergent problem among patients with epilepsy. However, little is known about interaction between MnSOD Ala16Val SNP and metabolic comorbities in epilepsy. Thus, we investigated the relationship between MnSOD Ala16Val SNP with epilepsy and its influence on MetS, inflammation, apoptosis and DNA damage parameters. Ninety subjects were evaluated (47 epilepsy patients and 43 healthy controls) by questionnaires and laboratorial exams. Levels of inflammatory, apoptotic and DNA damage markers, as well as MnSOD polymorphism were assessed. An increased proportion of VV genotype in epilepsy group when compared to control group was observed. Tumor Necrosis Factor-α (TNF-α), Acetylcholinesterase, caspase-8, and Picogreen levels were increased in VV epilepsy group. An important correlation between TNF-α vs caspase-8, and Cholesterol vs. Triglycerides was observed in the epilepsy group with VV genotype. Our findings suggest that the MnSOD Ala16Val SNP might have an important role in epilepsy, mainly in patients with generalized seizures and particularly with VV genotype. The metabolic parameters also presented significant results in epilepsy group with VV genotype, which applying attention in view of further consequences and disorders that could be developed.
Assuntos
Substituição de Aminoácidos , Colesterol/metabolismo , Convulsões/genética , Superóxido Dismutase/genética , Triglicerídeos/metabolismo , Acetilcolinesterase/genética , Adulto , Estudos de Casos e Controles , Caspase 8/genética , Dano ao DNA , Feminino , Proteínas Ligadas por GPI/genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Estresse Oxidativo , Fator de Necrose Tumoral alfa/genéticaRESUMO
The manganese-dependent superoxide dismutase (MnSOD) Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of vascular diseases. Brain-Derived Neurotrophic Factor (BDNF) plays an essential role in the plasticity and neuronal regeneration of the brain after vascular injuries. However, little is known about interaction between MnSOD Ala16Val SNP on stroke, a frequent neurologic disease that involves various interacting pathways, such as vascular dysfunctions, inflammation, and neurotrophic factors. In this sense, the objective of this study was to investigate the relationship between MnSOD Ala16Val SNP with BDNF levels on stroke and also its influence on nitrosative stress, inflammatory, apoptotic, and DNA damage parameters. For this, 88 subjects were investigated, 44 subjects poststroke and 44 healthy controls. Questionnaires were applied to clinical characteristics and after laboratorial exams were collected. We analyzed levels of oxidative/nitrosative stress, inflammatory, apoptotic, and DNA damage markers. We showed a higher proportion of VV genotype in poststroke as compared to healthy subjects. Nitrite/nitrate, Tumor Necrosis Factor-α, Caspase 3 (CASP 3) and 8 (CASP 8) activation, Acethylcholinesterase (AChE), and Picogreen levels were higher in VV poststroke group, as well as BDNF and ACh levels were lower in VV and AV poststroke. We may suggest that V allele carries a worse outcome profile after stroke, relating to nitrosative stress, inflammatory, and apoptotic response. These events associated to a BDNF reduction, probably, contribute to the appearance or reincidence of stroke.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Caspase 3/sangue , Caspase 8/sangue , Mediadores da Inflamação/sangue , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Superóxido Dismutase/genética , Fator de Necrose Tumoral alfa/sangue , Acetilcolinesterase/sangue , Idoso , Apoptose , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Crônica , Dano ao DNA , Regulação para Baixo , Feminino , Proteínas Ligadas por GPI/sangue , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/sangue , Nitritos/sangue , Estresse Nitrosativo , Fenótipo , Prognóstico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/enzimologiaRESUMO
Oxidized LDL (ox-LDL) is involved in the initiation and progression of atherosclerosis. Many factors can affect the LDL oxidation such as oxidative stress. The present study tested whether ox-LDL levels would be associated with apolipoprotein E (APOE), manganese superoxide dismutase (MnSOD) Ala16Val polymorphisms, and classic cardiovascular risk factors. ox-LDL levels were measured by thiobarbituric acid-reactive substances and both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism in a sample of 252 subjects (70 men, 182 women, mean age, 54-85 years). Subjects with ox-LDL >or=0.5 nmol/mg apoprotein were considered the high level group (HLG, N = 82) and subjects with ox-LDL <0.5 nmol/mg apoprotein were considered the expected level group (ELG, N = 170). Classic risk factors were also evaluated. The results showed that diabetes mellitus was more prevalent in HLG, whereas other cardiovascular risk factors were similar between groups. The APOE genotype frequencies did not differ between HLG and ELG subjects. However, AA genotype from MnSOD polymorphism was more frequent in ELG (chi(2) = 8.48; P = 0.014). AV and VV subjects from ELG present highest ox-LDL levels (OR = 3.61; CI95% = 1.42-9.17) than AA. Additional analysis did not find gene-gene interactions associated with ox-LDL levels. Multivariate analysis showed that diabetes and the MnSOD polymorphism were independent factors associated with higher ox-LDL levels in HLG. The results suggest that an important framework on modulation of the redox status influenced by genetic polymorphisms could affect the cardiovascular homeostasis.
