Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/129937 |
Resumo: | Introduction 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). |
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Souza, Bianca Marmontel deMichels, Marcus SilvaSortica, Denise AlvesBouças, Ana PaulaRheinheimer, JakelineBuffon, Marjoriê PiucoBauer, Andrea CarlaCanani, Luis Henrique SantosCrispim, Daisy2015-11-19T02:40:11Z20151932-6203http://hdl.handle.net/10183/129937000972540Introduction 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).application/pdfengPLoS ONE. San Francisco. Vol. 10, no. 7 (July 2015), e0132938, 15 p.Taxa de filtração glomerularDiabetes mellitus tipo 2Expressão gênicaRimPolymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidneyEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL000972540.pdf000972540.pdfTexto completo (inglês)application/pdf529329http://www.lume.ufrgs.br/bitstream/10183/129937/1/000972540.pdf24f543ab2786fdb52c65bd9ad577aaf4MD51TEXT000972540.pdf.txt000972540.pdf.txtExtracted Texttext/plain53039http://www.lume.ufrgs.br/bitstream/10183/129937/2/000972540.pdf.txt76992d530529bd0bdf3ef765ac48356aMD52THUMBNAIL000972540.pdf.jpg000972540.pdf.jpgGenerated Thumbnailimage/jpeg2032http://www.lume.ufrgs.br/bitstream/10183/129937/3/000972540.pdf.jpg22ba4e4e53cb38be5f77186129ebe74cMD5310183/1299372018-10-29 09:25:27.39oai:www.lume.ufrgs.br:10183/129937Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2018-10-29T12:25:27Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney |
title |
Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney |
spellingShingle |
Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney Souza, Bianca Marmontel de Taxa de filtração glomerular Diabetes mellitus tipo 2 Expressão gênica Rim |
title_short |
Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney |
title_full |
Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney |
title_fullStr |
Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney |
title_full_unstemmed |
Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney |
title_sort |
Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney |
author |
Souza, Bianca Marmontel de |
author_facet |
Souza, Bianca Marmontel de Michels, Marcus Silva Sortica, Denise Alves Bouças, Ana Paula Rheinheimer, Jakeline Buffon, Marjoriê Piuco Bauer, Andrea Carla Canani, Luis Henrique Santos Crispim, Daisy |
author_role |
author |
author2 |
Michels, Marcus Silva Sortica, Denise Alves Bouças, Ana Paula Rheinheimer, Jakeline Buffon, Marjoriê Piuco Bauer, Andrea Carla Canani, Luis Henrique Santos Crispim, Daisy |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Souza, Bianca Marmontel de Michels, Marcus Silva Sortica, Denise Alves Bouças, Ana Paula Rheinheimer, Jakeline Buffon, Marjoriê Piuco Bauer, Andrea Carla Canani, Luis Henrique Santos Crispim, Daisy |
dc.subject.por.fl_str_mv |
Taxa de filtração glomerular Diabetes mellitus tipo 2 Expressão gênica Rim |
topic |
Taxa de filtração glomerular Diabetes mellitus tipo 2 Expressão gênica Rim |
description |
Introduction 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). |
publishDate |
2015 |
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2015-11-19T02:40:11Z |
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2015 |
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1932-6203 |
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PLoS ONE. San Francisco. Vol. 10, no. 7 (July 2015), e0132938, 15 p. |
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