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rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: role in diabetic kidney disease

BACKGROUND: We carried out a case–control study in patients with type 2 diabetes mellitus (T2DM) to evaluate the association between seven single nucleotide polymorphisms (SNPs) previously described to be linked to diabetic kidney disease (DKD) in type 1 diabetes mellitus (T1DM). Additionally, we ev...

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Autores principales: Buffon, Marjoriê P., Carpena, Mariana P., Sortica, Denise A., Santer, Andressa, Carlessi, Rodrigo, de Souza, Bianca M., Edelweiss, Maria I., Berger, Milton, Crispim, Daisy, Canani, Luís H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706705/
https://www.ncbi.nlm.nih.gov/pubmed/26753002
http://dx.doi.org/10.1186/s13098-015-0121-5
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author Buffon, Marjoriê P.
Carpena, Mariana P.
Sortica, Denise A.
Santer, Andressa
Carlessi, Rodrigo
de Souza, Bianca M.
Edelweiss, Maria I.
Berger, Milton
Crispim, Daisy
Canani, Luís H.
author_facet Buffon, Marjoriê P.
Carpena, Mariana P.
Sortica, Denise A.
Santer, Andressa
Carlessi, Rodrigo
de Souza, Bianca M.
Edelweiss, Maria I.
Berger, Milton
Crispim, Daisy
Canani, Luís H.
author_sort Buffon, Marjoriê P.
collection PubMed
description BACKGROUND: We carried out a case–control study in patients with type 2 diabetes mellitus (T2DM) to evaluate the association between seven single nucleotide polymorphisms (SNPs) previously described to be linked to diabetic kidney disease (DKD) in type 1 diabetes mellitus (T1DM). Additionally, we evaluated gene and protein expression related to the polymorphism associated with DKD. METHODS: The association study included 1098 T2DM patients (718 with DKD and 380 without DKD). Out of the 13 polymorphisms associated with DKD in a previous study with T1DM, seven were chosen for evaluation in this sample: rs1888747, rs9521445, rs39075, rs451041, rs1041466, rs1411766 and rs6492208. The expression study included 91 patients who underwent nephrectomy. Gene expression was assessed by RT-qPCR and protein expression in kidney samples was quantified by western blot and it localization by immunohistochemistry. RESULTS: The C/C genotype of rs1888747 SNP was associated with protection for DKD (OR = 0.6, 95 % CI 0.3–0.9; P = 0.022). None of the other SNPs were associated with DKD. rs1888747 is located near FRMD3 gene. Therefore, FRMD3 gene and protein expression were evaluated in human kidney tissue according to rs1888747 genotypes. Gene and protein expression were similar in subjects homozygous for the C allele and in those carrying the G allele. CONCLUSIONS: Replication of the association between rs1888747 SNP and DKD in a different population suggests that this link is not the result of chance. rs1888747 SNP is located at the FRMD3 gene, which is expressed in human kidney. Therefore, this gene is a candidate gene for DKD. However, in this study, no rs1888747 genotype or specific allele effect on gene and/or protein expression of the FRMD3 gene was demonstrated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13098-015-0121-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-47067052016-01-10 rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: role in diabetic kidney disease Buffon, Marjoriê P. Carpena, Mariana P. Sortica, Denise A. Santer, Andressa Carlessi, Rodrigo de Souza, Bianca M. Edelweiss, Maria I. Berger, Milton Crispim, Daisy Canani, Luís H. Diabetol Metab Syndr Research BACKGROUND: We carried out a case–control study in patients with type 2 diabetes mellitus (T2DM) to evaluate the association between seven single nucleotide polymorphisms (SNPs) previously described to be linked to diabetic kidney disease (DKD) in type 1 diabetes mellitus (T1DM). Additionally, we evaluated gene and protein expression related to the polymorphism associated with DKD. METHODS: The association study included 1098 T2DM patients (718 with DKD and 380 without DKD). Out of the 13 polymorphisms associated with DKD in a previous study with T1DM, seven were chosen for evaluation in this sample: rs1888747, rs9521445, rs39075, rs451041, rs1041466, rs1411766 and rs6492208. The expression study included 91 patients who underwent nephrectomy. Gene expression was assessed by RT-qPCR and protein expression in kidney samples was quantified by western blot and it localization by immunohistochemistry. RESULTS: The C/C genotype of rs1888747 SNP was associated with protection for DKD (OR = 0.6, 95 % CI 0.3–0.9; P = 0.022). None of the other SNPs were associated with DKD. rs1888747 is located near FRMD3 gene. Therefore, FRMD3 gene and protein expression were evaluated in human kidney tissue according to rs1888747 genotypes. Gene and protein expression were similar in subjects homozygous for the C allele and in those carrying the G allele. CONCLUSIONS: Replication of the association between rs1888747 SNP and DKD in a different population suggests that this link is not the result of chance. rs1888747 SNP is located at the FRMD3 gene, which is expressed in human kidney. Therefore, this gene is a candidate gene for DKD. However, in this study, no rs1888747 genotype or specific allele effect on gene and/or protein expression of the FRMD3 gene was demonstrated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13098-015-0121-5) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-08 /pmc/articles/PMC4706705/ /pubmed/26753002 http://dx.doi.org/10.1186/s13098-015-0121-5 Text en © Buffon et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Buffon, Marjoriê P.
Carpena, Mariana P.
Sortica, Denise A.
Santer, Andressa
Carlessi, Rodrigo
de Souza, Bianca M.
Edelweiss, Maria I.
Berger, Milton
Crispim, Daisy
Canani, Luís H.
rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: role in diabetic kidney disease
title rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: role in diabetic kidney disease
title_full rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: role in diabetic kidney disease
title_fullStr rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: role in diabetic kidney disease
title_full_unstemmed rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: role in diabetic kidney disease
title_short rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: role in diabetic kidney disease
title_sort rs1888747 polymorphism in the frmd3 gene, gene and protein expression: role in diabetic kidney disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706705/
https://www.ncbi.nlm.nih.gov/pubmed/26753002
http://dx.doi.org/10.1186/s13098-015-0121-5
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