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dc.provenanceFacultad de Ciencias Exactas y Naturales de la UBA-
dc.contributorPenas-Steinhardt, A.-
dc.contributorBarcos, L.S.-
dc.contributorBelforte, F.S.-
dc.contributorde Sereday, M.-
dc.contributorVilariño, J.-
dc.contributorGonzalez, C.D.-
dc.contributorMartínez-Larrad, M.T.-
dc.contributorTellechea, M.L.-
dc.contributorSerrano-Ríos, M.-
dc.contributorPoskus, E.-
dc.contributorFrechtel, G.D.-
dc.contributorLeskow, F.C.-
dc.creatorPenas-Steinhardt, A.-
dc.creatorBarcos, L.S.-
dc.creatorBelforte, F.S.-
dc.creatorde Sereday, M.-
dc.creatorVilariño, J.-
dc.creatorGonzalez, C.D.-
dc.creatorMartínez-Larrad, M.T.-
dc.creatorTellechea, M.L.-
dc.creatorSerrano-Ríos, M.-
dc.creatorPoskus, E.-
dc.creatorFrechtel, G.D.-
dc.creatorLeskow, F.C.-
dc.date.accessioned2018-05-04T21:56:08Z-
dc.date.accessioned2018-05-28T15:49:13Z-
dc.date.available2018-05-04T21:56:08Z-
dc.date.available2018-05-28T15:49:13Z-
dc.date.issued2012-
dc.identifier.urihttp://10.0.0.11:8080/jspui/handle/bnmm/68620-
dc.descriptionSubclinical low-grade systemic inflammation has been associated with obesity, insulin resistance and metabolic syndrome (MS). Recent studies have highlighted the role of gut microbiota in these disorders. The toll-like receptor 4 (TLR4) plays a key role in the innate immune response activation. We studied two polymorphisms (+3725G/C and 11350G/C) in the 3′ untranslated region (3′UTR) of the TLR4 gene that may alter its expression and their association with metabolic disorders related to systemic inflammation. We cloned the 3′UTR into a luciferase reporter system and compared wild-type 3′UTR (WT) and +3725C variant (MUT) constructs luciferase activities. MUT construct reduced the reporter gene activity by 30% compared to WT (P = 0.0001). To evaluate the association between these polymorphisms with biochemical and clinical overweight related variables, we conducted a population cross-sectional study in 966 men of Argentine general population. Considering smoking as a confounding variable that causes systemic inflammation, we studied these possible effects in both, smokers and nonsmokers. The 11350G/C polymorphism was not detected in our sample whereas the CC genotype of +3725 polymorphism was associated with lean subjects (p = 0.011) and higher Adiponectin levels (p = 0.021). Subjects without any NCEP/ATP III MS component were associated with this genotype as well (p = 0.001). These results were strengthened in nonsmokers, in which CC genotype was associated with lean subjects (p = 0.003) and compared with G carriers showed significantly lower BMI (25.53 vs. 28.60 kg/m2; p = 0.023) and waist circumference (89.27 vs. 97.51 cm; p = 0.025). None of these associations were found in smokers. These results showed that +3725C variant has a functional effect down-regulating gene expression and it could be considered as a predictive factor against overweight, particularly in nonsmokers. Considering the role of TLR4 in inflammation, these findings would suggest that the presence of +3725C variant could predict a lower prevalence of chronic metabolic disorders. © 2012 Penas-Steinhardt et al.-
dc.formatapplication/pdf-
dc.languageeng-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.rightshttp://creativecommons.org/licenses/by/2.5/ar-
dc.sourcePLoS ONE 2012;7(12)-
dc.source.urihttp://digital.bl.fcen.uba.ar/Download/paper/paper_19326203_v7_n12_p_PenasSteinhardt.pdf-
dc.subjectadiponectin-
dc.subjectcysteine-
dc.subjectglycine-
dc.subjectluciferase-
dc.subjectmessenger RNA-
dc.subjecttoll like receptor 4-
dc.subject3' untranslated region-
dc.subjectadult-
dc.subjectArgentina-
dc.subjectarticle-
dc.subjectbody mass-
dc.subjectcross-sectional study-
dc.subjectdown regulation-
dc.subjectenzyme activity-
dc.subjectethnic group-
dc.subjectgene activity-
dc.subjectgene expression regulation-
dc.subjectgene frequency-
dc.subjectgene function-
dc.subjectgenetic analysis-
dc.subjectgenetic association-
dc.subjectgenetic stability-
dc.subjectgenetic variability-
dc.subjectgenotype-
dc.subjectheterozygote-
dc.subjecthuman-
dc.subjectinflammation-
dc.subjectlean body weight-
dc.subjectmajor clinical study-
dc.subjectmale-
dc.subjectmolecular cloning-
dc.subjectobesity-
dc.subjectpopulation research-
dc.subjectprediction-
dc.subjectprotection-
dc.subjectregulator gene-
dc.subjectreporter gene-
dc.subjectsingle nucleotide polymorphism-
dc.subjectsmoking habit-
dc.subjectsystemic disease-
dc.subjecttoll like receptor 4 gene-
dc.subjectwaist circumference-
dc.subjectwild type-
dc.subject3' Untranslated Regions-
dc.subjectAdiponectin-
dc.subjectAdult-
dc.subjectGene Expression Regulation-
dc.subjectGenetic Association Studies-
dc.subjectHumans-
dc.subjectImmunity, Innate-
dc.subjectInsulin Resistance-
dc.subjectMale-
dc.subjectMetabolic Syndrome X-
dc.subjectObesity-
dc.subjectOverweight-
dc.subjectPolymorphism, Single Nucleotide-
dc.subjectSmoking-
dc.subjectToll-Like Receptor 4-
dc.titleFunctional Characterization of TLR4 +3725 G/C Polymorphism and Association with Protection against Overweight-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:ar-repo/semantics/artículo-
dc.typeinfo:eu-repo/semantics/publishedVersion-
Aparece en las colecciones: FCEN - Facultad de Ciencias Exactas y Naturales. UBA

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