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What Is the Contribution of Two Genetic Variants Regulating VEGF Levels to Type 2 Diabetes Risk and to Microvascular Complications?

Vascular endothelial growth factor (VEGF) is a key chemokine involved in tissue growth and organ repair processes, particularly angiogenesis. Elevated circulating VEGF levels are believed to play a role in type 2 diabetes (T2D) microvascular complications, especially diabetic retinopathy. Recently,...

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Autores principales: Bonnefond, Amélie, Saulnier, Pierre-Jean, Stathopoulou, Maria G., Grarup, Niels, Ndiaye, Ndeye Coumba, Roussel, Ronan, Nezhad, Mohsen Azimi, Dechaume, Aurélie, Lantieri, Olivier, Hercberg, Serge, Lauritzen, Torsten, Balkau, Beverley, El-Sayed Moustafa, Julia S., Hansen, Torben, Pedersen, Oluf, Froguel, Philippe, Charpentier, Guillaume, Marre, Michel, Hadjadj, Samy, Visvikis-Siest, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566098/
https://www.ncbi.nlm.nih.gov/pubmed/23405237
http://dx.doi.org/10.1371/journal.pone.0055921
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author Bonnefond, Amélie
Saulnier, Pierre-Jean
Stathopoulou, Maria G.
Grarup, Niels
Ndiaye, Ndeye Coumba
Roussel, Ronan
Nezhad, Mohsen Azimi
Dechaume, Aurélie
Lantieri, Olivier
Hercberg, Serge
Lauritzen, Torsten
Balkau, Beverley
El-Sayed Moustafa, Julia S.
Hansen, Torben
Pedersen, Oluf
Froguel, Philippe
Charpentier, Guillaume
Marre, Michel
Hadjadj, Samy
Visvikis-Siest, Sophie
author_facet Bonnefond, Amélie
Saulnier, Pierre-Jean
Stathopoulou, Maria G.
Grarup, Niels
Ndiaye, Ndeye Coumba
Roussel, Ronan
Nezhad, Mohsen Azimi
Dechaume, Aurélie
Lantieri, Olivier
Hercberg, Serge
Lauritzen, Torsten
Balkau, Beverley
El-Sayed Moustafa, Julia S.
Hansen, Torben
Pedersen, Oluf
Froguel, Philippe
Charpentier, Guillaume
Marre, Michel
Hadjadj, Samy
Visvikis-Siest, Sophie
author_sort Bonnefond, Amélie
collection PubMed
description Vascular endothelial growth factor (VEGF) is a key chemokine involved in tissue growth and organ repair processes, particularly angiogenesis. Elevated circulating VEGF levels are believed to play a role in type 2 diabetes (T2D) microvascular complications, especially diabetic retinopathy. Recently, a genome-wide association study identified two common single nucleotide polymorphisms (SNPs; rs6921438 and rs10738760) explaining nearly half of the variance in circulating VEGF levels. Considering the putative contribution of VEGF to T2D and its complications, we aimed to assess the effect of these VEGF-related SNPs on the risk of T2D, nephropathy and retinopathy, as well as on variation in related traits. SNPs were genotyped in several case-control studies: French and Danish T2D studies (N(cases) = 6,920-N(controls) = 3,875 and N(cases) = 3,561-N(controls) = 2,623; respectively), two French studies one for diabetic nephropathy (N(cases) = 1,242-N(controls) = 860) and the other for diabetic retinopathy (N(cases) = 1,336-N(controls) = 1,231). The effects of each SNP on quantitative traits were analyzed in a French general population-based cohort (N = 4,760) and two French T2D studies (N = 3,480). SNP associations were assessed using logistic or linear regressions. In the French population, we found an association between the G-allele of rs6921438, shown to increase circulating VEGF levels, and increased T2D risk (OR = 1.15; P = 3.7×10(−5)). Furthermore, the same allele was associated with higher glycated hemoglobin levels (β = 0.02%; P = 9.2×10(−3)). However, these findings were not confirmed in the Danes. Conversely, the SNP rs10738760 was not associated with T2D in the French or Danish populations. Despite having adequate statistical power, we did not find any significant effects of rs6921438 or rs10738760 on diabetic microvascular complications or the variation in related traits in T2D patients. In spite of their impact on the variance in circulating VEGF, we did not find any association between SNPs rs6921438 and rs10738760, and the risk of T2D, diabetic nephropathy or retinopathy. The link between VEGF and T2D and its complications might be indirect and more complex than expected.
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spelling pubmed-35660982013-02-12 What Is the Contribution of Two Genetic Variants Regulating VEGF Levels to Type 2 Diabetes Risk and to Microvascular Complications? Bonnefond, Amélie Saulnier, Pierre-Jean Stathopoulou, Maria G. Grarup, Niels Ndiaye, Ndeye Coumba Roussel, Ronan Nezhad, Mohsen Azimi Dechaume, Aurélie Lantieri, Olivier Hercberg, Serge Lauritzen, Torsten Balkau, Beverley El-Sayed Moustafa, Julia S. Hansen, Torben Pedersen, Oluf Froguel, Philippe Charpentier, Guillaume Marre, Michel Hadjadj, Samy Visvikis-Siest, Sophie PLoS One Research Article Vascular endothelial growth factor (VEGF) is a key chemokine involved in tissue growth and organ repair processes, particularly angiogenesis. Elevated circulating VEGF levels are believed to play a role in type 2 diabetes (T2D) microvascular complications, especially diabetic retinopathy. Recently, a genome-wide association study identified two common single nucleotide polymorphisms (SNPs; rs6921438 and rs10738760) explaining nearly half of the variance in circulating VEGF levels. Considering the putative contribution of VEGF to T2D and its complications, we aimed to assess the effect of these VEGF-related SNPs on the risk of T2D, nephropathy and retinopathy, as well as on variation in related traits. SNPs were genotyped in several case-control studies: French and Danish T2D studies (N(cases) = 6,920-N(controls) = 3,875 and N(cases) = 3,561-N(controls) = 2,623; respectively), two French studies one for diabetic nephropathy (N(cases) = 1,242-N(controls) = 860) and the other for diabetic retinopathy (N(cases) = 1,336-N(controls) = 1,231). The effects of each SNP on quantitative traits were analyzed in a French general population-based cohort (N = 4,760) and two French T2D studies (N = 3,480). SNP associations were assessed using logistic or linear regressions. In the French population, we found an association between the G-allele of rs6921438, shown to increase circulating VEGF levels, and increased T2D risk (OR = 1.15; P = 3.7×10(−5)). Furthermore, the same allele was associated with higher glycated hemoglobin levels (β = 0.02%; P = 9.2×10(−3)). However, these findings were not confirmed in the Danes. Conversely, the SNP rs10738760 was not associated with T2D in the French or Danish populations. Despite having adequate statistical power, we did not find any significant effects of rs6921438 or rs10738760 on diabetic microvascular complications or the variation in related traits in T2D patients. In spite of their impact on the variance in circulating VEGF, we did not find any association between SNPs rs6921438 and rs10738760, and the risk of T2D, diabetic nephropathy or retinopathy. The link between VEGF and T2D and its complications might be indirect and more complex than expected. Public Library of Science 2013-02-06 /pmc/articles/PMC3566098/ /pubmed/23405237 http://dx.doi.org/10.1371/journal.pone.0055921 Text en © 2013 Bonnefond et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bonnefond, Amélie
Saulnier, Pierre-Jean
Stathopoulou, Maria G.
Grarup, Niels
Ndiaye, Ndeye Coumba
Roussel, Ronan
Nezhad, Mohsen Azimi
Dechaume, Aurélie
Lantieri, Olivier
Hercberg, Serge
Lauritzen, Torsten
Balkau, Beverley
El-Sayed Moustafa, Julia S.
Hansen, Torben
Pedersen, Oluf
Froguel, Philippe
Charpentier, Guillaume
Marre, Michel
Hadjadj, Samy
Visvikis-Siest, Sophie
What Is the Contribution of Two Genetic Variants Regulating VEGF Levels to Type 2 Diabetes Risk and to Microvascular Complications?
title What Is the Contribution of Two Genetic Variants Regulating VEGF Levels to Type 2 Diabetes Risk and to Microvascular Complications?
title_full What Is the Contribution of Two Genetic Variants Regulating VEGF Levels to Type 2 Diabetes Risk and to Microvascular Complications?
title_fullStr What Is the Contribution of Two Genetic Variants Regulating VEGF Levels to Type 2 Diabetes Risk and to Microvascular Complications?
title_full_unstemmed What Is the Contribution of Two Genetic Variants Regulating VEGF Levels to Type 2 Diabetes Risk and to Microvascular Complications?
title_short What Is the Contribution of Two Genetic Variants Regulating VEGF Levels to Type 2 Diabetes Risk and to Microvascular Complications?
title_sort what is the contribution of two genetic variants regulating vegf levels to type 2 diabetes risk and to microvascular complications?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566098/
https://www.ncbi.nlm.nih.gov/pubmed/23405237
http://dx.doi.org/10.1371/journal.pone.0055921
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