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Rasmussen L.,Laboratorio Of Genetica | Rasmussen L.,Federal University of Sao Paulo | Mazzotti D.,Federal University of Sao Paulo | Bertolucci P.-H.,Federal University of Sao Paulo | And 7 more authors.
Journal of Alzheimer's Disease | Year: 2013

Alzheimer's disease (AD) is a progressive neurodegenerative disease that takes the form of a local overexpression of cytokines and other inflammatory molecules. We investigated three single-nucleotide polymorphisms (SNP) of the interleukin 6 gene (IL-6) promoter region [-174G/C (rs 1800795), -572C/G (rs 1800796), and -597G/A (rs 1800797)] in 200 patients with late-onset AD and 165 elderly controls in a Brazilian case-control population sample. Genotyping was carried out from blood cells using PCR-RFLP techniques. Statistical analysis was performed to evaluate the Hardy-Weinberg equilibrium and to compare frequencies between groups. No association was found between any IL-6 polymorphism and AD; however the haplotype composed of the -597 A allele and the -174G allele indicated a crude odds ratio (OR) of 0.15 (p = 0.0021) and a significantly adjusted OR (adjusted for the APOE E4 allele value) of 0.15 (p = 0.00294). Linkage disequilibrium was D' = 0.68 among the three SNPs. Our findings revealed a protective effect of AG (-597A, -174G) haplotype, which worked independently of the APOE E4 allele in our Brazilian population sample. Thus, the promoter region of IL-6 gene probably exerts an effect through gene linkage and/or gene interaction. © 2013 - IOS Press and the authors. All rights reserved. Source


Vendramini A.A.,Sacred Heart University of Brazil | de Labio R.W.,Disciplina de Genetica | Rasmussen L.T.,Disciplina de Genetica | Rasmussen L.T.,University of Sao Paulo | And 9 more authors.
Genetics and Molecular Biology | Year: 2011

An inflammatory process has been involved in numerous neurodegenerative disorders such as Parkinson's disease, stroke and Alzheimer's disease (AD). In AD, the inflammatory response is mainly located in the vicinity of amyloid plaques. Cytokines, such as interleukin-8 (IL-8) and interleukin-1α (IL-1α), have been clearly involved in this inflammatory process. Polymorphisms of several interleukin genes have been correlated to the risk of developing AD. The present study investigated the association of AD with polymorphisms IL-8 -251T > A (rs4073) and IL-1α-889C > T (rs1800587) and the interactive effect of both, adjusted by the Apolipoprotein E genotype. 199 blood samples from patients with AD, 146 healthy elderly controls and 95 healthy young controls were obtained. DNA samples were isolated from blood cells, and the PCR-RFLP method was used for genotyping. The genotype distributions of polymorphisms IL-8, IL-1α and APOE were as expected under Hardy-Weinberg equilibrium. The allele frequencies did not differ significantly among the three groups tested. As expected, the APOE4 allele was strongly associated with AD (p < 0.001). No association of AD with either the IL-1α or the IL-8 polymorphism was observed, nor was any interactive effect between both polymorphisms. These results confirm previous studies in other populations, in which polymorphisms IL-8 -251T > A and IL-1α-889C > T were not found to be risk factors for AD. © 2011, Sociedade Brasileira de Genética. Source


Ferreira R.F.,Nucleo de Pesquisa em Bioquimica e Biologia Molecular | Nogueira V.,Nucleo de Pesquisa em Bioquimica e Biologia Molecular | Pinhel M.A.S.,Nucleo de Pesquisa em Bioquimica e Biologia Molecular | Tenani G.D.,Nucleo de Pesquisa em Bioquimica e Biologia Molecular | And 3 more authors.
Genetics and Molecular Research | Year: 2015

We evaluated the influence of the vascular endothelial growth factor (VEGF) -C936T polymorphism on prognosis of hepatocellular carcinoma (HCC), cirrhosis, and hepatitis C virus (HCV) infection. Serum VEGF and alpha-fetoprotein (AFP) levels were determined and used to characterize sensitivity and specificity. A total of 285 subjects were studied: 68 HCC, 118 cirrhosis, 43 HCV, and 56 healthy controls. Prevalence of the VEGF -C936T polymorphism and serum levels of VEGF and AFP were analyzed by polymerase chain reaction-restriction fragment length polymorphism and enzyme-linked immunosorbent assay, respectively. The genotype CC (frequencies between 63.24 and 76.79%; P > 0.05) and the C allele (absolute frequencies from 0.816 to 0.884, P > 0.05) were prevalent in all groups. Higher VEGF levels in HCC patients (588.0 ± 501.0 pg/mL) were observed, particularly in patients with the T allele in VEGF -C936T (764.4 ± 571.7 pg/mL) compared to those in the other groups (P < 0.05). The same trend occurred with AFP levels (HCC = 8.522 ± 23.830; cirrhosis = 12.7 ± 59.3; HCV = 4.6 ± 4.7; control = 2.7 ± 1.8 ng/mL; P = 0.005). Levels of VEGF and AFP showed sensitivity of 65 and 28% and specificity of 85 and 99%, respectively, for HCC patients. In conclusion, the VEGF -C936T polymorphism is not associated with HCC but the mutant allele (T) increases VEGF levels in HCC patients. VEGF could be a potential biomarker for HCC, while AFP could be used to distinguish between patients with HCC and cirrhosis or HCV. © FUNPEC-RP. Source


Valsoni B.C.G.,Sao Paulo State University | Bonfim M.R.,Sao Paulo State University | Camargo R.C.T.,Sao Paulo State University | de Abreu L.C.,Laboratorio Of Delineamento Of Estudos E Escrita Cientifica Na | And 2 more authors.
International Journal of Morphology | Year: 2015

The objective of this study was to analyze the effects of passive smoking, in soleus and gastrocnemius muscles associated with physical exercise by swimming during pregnancy and lactation of rats. Twenty-four rats were divided: GF (exposed to cigarette smoke), GC (control), GFN (underwent to the swimming program and exposed to cigarette smoke) and GN (underwent to the swimming program). On the first day of pregnancy procedure of exposure to cigarette smoke began, consisting in 30 minutes twice a day for six weeks. During the same period the swimming program began, which lasted 60 min every day untilthe 21st day of lactation. Soleus and gastrocnemius muscles, were obtained for histological, histochemical, morphometric analysis and fiber profiling. In histology, the groups GF and GFN showed infiltrations, necrotic and phagocytized fibers, centralized nuclei, splittings and coiling; in GN changes were observed due to exercise adaptations, infiltrations, sarcolemal lesion, polymorphic, atrophic and angular fibers. In the histochemical analysis of the groups GF and GFN there was enzymatic activity and amorphous formazan aggregates in subsarcolemmal positions, however in GN the same changes were found in lower frequency and intensity. In regard to the measure of the cross-section of muscle fibers there weren’t significant differences among the groups, as well as, in the frequency of types of fibers of the gastrocnemius. It is concluded that aerobic exercise is not enough to impede morphological and histochemical changes caused in an animal model of pregnant and lactating associated with smoking, and the stress not influence the types and size of muscle fibers. © 2015, Universidad de la Frontera. All rights reserved. Source

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