Common Sequence Variation in the<i>VEGFA</i>Gene Predicts Risk of Diabetic Retinopathy

Abhary, Sotoodeh; Burdon, Kathryn P.; Gupta, Aanchal; Lake, Stewart; Selva, Dinesh; Petrovsky, Nikolai; Craig, Jamie E

doi:10.1167/iovs.09-3694

Cited by 61 publications

(62 citation statements)

References 50 publications

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“…The study selection process is shown in figure 1. A total of 9 studies examined the association between the VEGF -2578C/A polymorphism and DR [13,14,15,16,17,18,19,20,21]. Of these, 3 studies for which the data was unavailable were excluded [19,20,21].…”

Section: Resultsmentioning

confidence: 99%

“…Of these, 3 studies for which the data was unavailable were excluded [19,20,21]. Thus, 6 studies were included in the current meta-analysis [13,14,15,16,17,18]. …”

Section: Resultsmentioning

confidence: 99%

“…Several single-nucleotide polymorphisms (SNPs) have been described in the VEGF gene, some of which have been reported to be associated with differential expression of VEGF in vitro [12]. VEGF SNPs have been investigated for a possible role in mediating genetic predisposition to DR. To this date, one of the SNPs which have been investigated a lot is -2578C/A polymorphism (rs699947) [13,14,15,16,17,18,19,20,21]. This SNP is located in the VEGF gene promoter.…”

Section: Introductionmentioning

confidence: 99%

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Meta-Analysis of Association between the -2578C/A Polymorphism of the Vascular Endothelial Growth Factor and Retinopathy in Type 2 Diabetes in Asians and Caucasians

Wang

Cheng²,

Zhu³

et al. 2014

Ophthalmic Res

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Background and Objectives: Vascular endothelial growth factor (VEGF) has been shown to play an important role in the development and progress of diabetic retinopathy (DR). A number of case-control studies focused on the association between VEGF -2578C/A and risk for DR. But the results were not always consistent, so we performed a meta-analysis to evaluate the precise association between this variant and risk for DR. Methods: All publications on the association between VEGF -2578C/A polymorphism and DR were searched in the following electronic databases: PubMed, Embase, the Cochrane Library and Chinese Biomedical Literature Database, with the last report up to January 2013. This meta-analysis was assessed by Review Manager 5.1. Results: A total of 6 studies were involved in this meta-analysis, including 835 cases and 867 controls. Overall, we found a significant association between this polymorphism and DR (A vs. C: OR = 1.49, 95% CI = 1.26-1.77, p < 0.00001; AA vs. CA + CC: OR = 1.26, 95% CI = 0.94-1.68, p = 0.12; AA + CA vs. CC: OR = 1.56, 95% CI = 1.27-1.91, p < 0.00001; AA vs. CC: OR = 1.67, 95% CI = 1.20-2.32, p = 0.003; CA vs. CC: OR = 1.51, 95% CI = 1.21-1.87, p = 0.0002), but we did not find any significant association in Caucasians in subgroup analysis. The results were not materially altered after the studies which did not fulfill the Hardy-Weinberg equilibrium were excluded. Conclusion: Our meta-analysis supports the association between the VEGF -2578C/A polymorphism and DR, but not in the Caucasian population.

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Section: Resultsmentioning

confidence: 99%

“…Of these, 3 studies for which the data was unavailable were excluded [19,20,21]. Thus, 6 studies were included in the current meta-analysis [13,14,15,16,17,18]. …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Meta-Analysis of Association between the -2578C/A Polymorphism of the Vascular Endothelial Growth Factor and Retinopathy in Type 2 Diabetes in Asians and Caucasians

Wang

Cheng²,

Zhu³

et al. 2014

Ophthalmic Res

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“…VEGF is believed to play a significant role in the development of diabetic complications. VEGFA variants were associated with the development of diabetic retinopathy [46,47] . Ginsenoside Rb1 obviously enhanced the expression of VEGF and enhanced myocardial angiogenesis [48] .…”

Section: Discussionmentioning

confidence: 99%

Deciphering the therapeutic mechanisms of Xiao-Ke-An in treatment of type 2 diabetes in mice by a Fangjiomics approach

et al. 2015

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Aim: Xiao-Ke-An (XKA) is a traditional Chinese medicine (TCM) formula for the treatment of type 2 diabetes (T2D), and the effective ingredients and their targets as well as the mechanisms of XKA remain to be elucidated. In this study we investigated the therapeutic mechanisms of XKA in the treatment of T2D in mice using a Fangjiomics approach. Methods: KKAy mice feeding on a high-fat diet were used as models of T2D, and were orally treated with XKA (0.75 or 1.5 g·kg -1 ·d -1 ) for 32 d. Microarray mRNA expression data were obtained from the livers of the mice. Differentially expressed genes (DEGs) were identified by reverse rate analysis and ANOVA analysis. The compounds in XKA were identified by LC-MS analysis or collected from TCM databases. The relationships between the compounds and targets were established by combining the DEGs with information derived from mining literature or herb target databases. Relevant pathways were identified through a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using WebGestalt. Results: The compound-target-pathway network based on compounds identified by LC-MS analysis (NCA) included 20 constituent compounds, 46 targets and 36 T2D-related pathways, whereas the compound-target-pathway network based on compounds collected from databases (NCD) consisted of 40 compounds, 68 targets and 21 pathways. In the treatment of T2D, XKA might act mainly by improving carbohydrate and lipid metabolism, as well as ameliorating insulin resistance, inflammation and diabetic vascular complications. Conclusion: The network-based approach reveals complex therapeutic mechanisms of XKA in the treatment of T2D in mice that involve numerous compounds, targets, and signaling pathways.

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“…To date, many studies have investigated the associations between polymorphisms in the VEGFA gene and DR. -634G/C (+405G/C or rs2010963) polymorphism in the 5′-untranslated region and-2578C/A (−2549I/D (in high linkage disequilibrium with -2578C/A) or rs699947) polymorphism in the promoter region of the VEGFA gene are most frequently investigated. However, the results have been inconsistent [5][6][7][8][9][10][11][12][13][14][15][16]. To date, three relevant meta-analyses [17][18][19] have published.…”

Section: Introductionmentioning

confidence: 99%

Two Polymorphisms (Rs699947, Rs2010963) in the VEGFA Gene and Diabetic Retinopathy: An Updated Meta-Analysis

Lu¹

2012

J Diabetes Metab

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Background: The vascular endothelial growth factor (VEGFA) gene has been suggested to play an important role in the pathogenesis of diabetic retinopathy (DR). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations between VEGFA polymorphisms and DR risk. Methods: Published literature from PubMed, EMBASE, Web of Science and Google Scholar were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-or random-effects model. Results: A total of eight studies (1204 cases and 1198 controls) for rs699947 polymorphism and ten studies (1666 cases and 1782 controls) for rs2010963 polymorphism were included in the meta-analysis. The results suggested that rs699947 polymorphism was marginally associated with DR under a homogeneous co-dominant model (AA vs. CC: OR = 1.69, 95% CI = 1.03-2.77, p = 0.040) and a dominant model (AA + AC vs. CC: OR = 1.38, 95% CI = 1.01-1.90, p = 0.040), whereas the association between rs2010963 polymorphism and DR was not significant under all genetic models (all p > 0.05). In the subgroup analysis, the effect size for rs699947 polymorphism was only marginally significant among European populations under a dominant model (OR = 1.47, 95% CI = 1.07-2.02, p = 0.018), but not among East Asians. After exclusion of outliers which were the source of between-study heterogeneity, there was significant association between rs699947 polymorphism and DR under a homogeneous co-dominant model (OR = 1.64, 95% CI = 1.18-2.28, p = 0.003), even after multiple comparison correction. Conclusions: Our meta-analysis confirmed the significant association between rs699947 polymorphism and DR after exclusion of outliers, and rs2010963 polymorphism might be not associated with DR.

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Common Sequence Variation in theVEGFAGene Predicts Risk of Diabetic Retinopathy

Abstract: Sequence variation in the VEGFA gene is associated with risk of developing blinding DR in T1DM and T2DM. Identifying specific genetic markers will allow for refined screening algorithms and earlier intervention in patients at highest risk.

Cited by 61 publications

References 50 publications

Meta-Analysis of Association between the -2578C/A Polymorphism of the Vascular Endothelial Growth Factor and Retinopathy in Type 2 Diabetes in Asians and Caucasians

Meta-Analysis of Association between the -2578C/A Polymorphism of the Vascular Endothelial Growth Factor and Retinopathy in Type 2 Diabetes in Asians and Caucasians

Deciphering the therapeutic mechanisms of Xiao-Ke-An in treatment of type 2 diabetes in mice by a Fangjiomics approach

Two Polymorphisms (Rs699947, Rs2010963) in the VEGFA Gene and Diabetic Retinopathy: An Updated Meta-Analysis

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