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dc.contributor.authorSouza, Bianca Marmontel dept_BR
dc.contributor.authorMichels, Marcus Silvapt_BR
dc.contributor.authorSortica, Denise Alvespt_BR
dc.contributor.authorBouças, Ana Paulapt_BR
dc.contributor.authorRheinheimer, Jakelinept_BR
dc.contributor.authorBuffon, Marjoriê Piucopt_BR
dc.contributor.authorBauer, Andrea Carlapt_BR
dc.contributor.authorCanani, Luis Henrique Santospt_BR
dc.contributor.authorCrispim, Daisypt_BR
dc.date.accessioned2015-11-19T02:40:11Zpt_BR
dc.date.issued2015pt_BR
dc.identifier.issn1932-6203pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/129937pt_BR
dc.description.abstractIntroduction Uncoupling protein 2 (UCP2) reduces production of reactive oxygen species (ROS) by mitochondria. ROS overproduction is one of the major contributors to the pathogenesis of chronic diabetic complications, such as diabetic kidney disease (DKD). Thus, deleterious polymorphisms in the UCP2 gene are candidate risk factors for DKD. In this study, we investigated whether UCP2 -866G/A, Ala55Val and Ins/Del polymorphisms were associated with DKD in patients with type 2 diabetes mellitus (T2DM), and whether they had an effect on UCP2 gene expression in human kidney tissue biopsies. Materials and Methods In a case-control study, frequencies of the UCP2 -866G/A, Ala55Val and Ins/Del polymorphisms as well as frequencies of the haplotypes constituted by them were analyzed in 287 T2DM patients with DKD and 281 T2DM patients without this complication. In a cross-sectional study, UCP2 gene expression was evaluated in 42 kidney biopsy samples stratified according to the presence of the UCP2 mutated -866A/55Val/Ins haplotype Results In the T2DM group, multivariate logistic regression analysis showed that the -866A/55Val/ Ins haplotype was an independent risk factor for DKD (OR = 2.136, 95% CI 1.036–4.404), although neither genotype nor allele frequencies of the individual polymorphisms differed between case and control groups. Interestingly, T2DM patients carrying the mutated haplotype showed decreased estimated glomerular filtration rate (eGFR) when compared to subjects with the reference haplotype (adjusted P= 0.035). In kidney biopsy samples, UCP2expression was significantly decreased in UCP2 mutated haplotype carriers when compared to kidneys from patients with the reference haplotype (0.32 ± 1.20 vs. 1.85 ± 1.16 n fold change; adjusted P< 0.000001).en
dc.format.mimetypeapplication/pdf
dc.language.isoengpt_BR
dc.relation.ispartofPLoS ONE. San Francisco. Vol. 10, no. 7 (July 2015), e0132938, 15 p.pt_BR
dc.rightsOpen Accessen
dc.subjectTaxa de filtração glomerularpt_BR
dc.subjectDiabetes mellitus tipo 2pt_BR
dc.subjectExpressão gênicapt_BR
dc.subjectRimpt_BR
dc.titlePolymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidneypt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb000972540pt_BR
dc.type.originEstrangeiropt_BR


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