A common variant highly associated with plasma VEGFA levels also contributes to the variation of both LDL-C and HDL-C

Stathopoulou, Maria G.; Bonnefond, Amélie; Ndiaye, Ndeye Coumba; Azimi‐Nezhad, Mohsen; Shamieh, Said El; Saleh, Abdelsalam; Rancier, Marc; Siest, Gérard; Lamont, John; Fitzgerald, Peter; Visvikis‐Siest, Sophie

doi:10.1194/jlr.p030551

Cited by 30 publications

(30 citation statements)

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“…The most influential SNP in this MR study of VEGF on IHD is rs6921438 ( LOC100132354 ), which is located downstream of VEGF and close to C6orf23 but encodes a currently uncharacterized protein, so it is difficult to know why it is relevant; rs6921438 might also be related to lipids, although the P values did not reach genome‐wide significance (1.2×10 −7 for high‐density lipoprotein cholesterol and 1.5×10 −4 for low‐density lipoprotein cholesterol) . Some of the gene regions including the other VEGF‐related SNPs are associated with other phenotypes .…”

Section: Discussionmentioning

confidence: 91%

Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study

Yeung

Lam

Schooling

2017

JAHA

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BackgroundVascular endothelial growth factor (VEGF) has angiogenic and possibly proatherosclerotic properties. Observationally it is positively associated with cardiovascular disease, although these observations could be confounded or due to reverse causation. We assessed ischemic heart disease (IHD) risk by genetically predicted VEGF, ie, using Mendelian randomization.Methods and ResultsSingle nucleotide polymorphisms (SNPs) predicting VEGF level, at genome‐wide significance, were applied to the CARDIoGRAMplusC4D 1000 Genomes‐based genome‐wide association study IHD case (n=60 801)‐control (n=123 504) study. We obtained unconfounded estimates using instrumental variable analysis by combining the Wald estimates for each SNP using inverse variance weighting and Mendelian randomization–Egger regression. Based on 9 SNPs independently predicting VEGF (rs1740073 [C6orf223], rs2375981 [KCNV2], rs2639990 [ZADH2], rs4782371 [ZFPM1], rs6921438 [LOC100132354], rs7043199 [VLDLR‐AS1], rs10761741 [JMJD1C], rs6993770 [ZFPM2], and rs114694170 [MEF2C]), VEGF was unrelated to IHD (odds ratio 0.99 per log‐transformed pg/mL, 95%CI 0.96‐1.02) using inverse variance weighting. However, Mendelian randomization–Egger regression suggested an inverse relation of VEGF with IHD (odds ratio 0.95, 95%CI 0.91‐0.99), although the association was not evident after excluding the lead SNP (rs6921438) or additionally excluding the pleiotropic SNP (rs6993770).ConclusionsOur study does not provide strong evidence for a positive effect of VEGF on IHD but does not rule out the possibility that some specific types of VEGF, for which genetic predictors have not yet been identified, might play a role.

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Section: Discussionmentioning

confidence: 91%

Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study

Yeung

Lam

Schooling

2017

JAHA

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“…Since functional SNPs of the VEGF gene are reported to affect the expression of this protein in cancer cells, these SNPs may be associated with increasing the tumor angiogenic activity and accelerating the process of carcinogenesis [21][22][23][24]. VEGF −2578C/A and +460T/C located in the promoter region, +1612G/A and +936C/T located in the 3′-untranslated region, and −634G/C located in the 5′-untranslated region are reported to have a role in influencing the plasma VEGF levels [30].…”

Section: Discussionmentioning

confidence: 99%

Predictive value of vascular endothelial growth factor polymorphisms on the risk of renal cell carcinomas: a case–control study

Dong

Zhang

et al. 2015

Tumor Biol.

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We conducted this case-control study to assess the role of vascular endothelial growth factor (VEGF) -2578C/A, +460T/C, +1612G/A, +936C/T, and -634G/C polymorphisms in the development of renal cell carcinoma (RCC), and analyzed the association of gene polymorphisms with demographic and clinical characteristics of RCC. This study included 412 consecutive primary RCC patients and 824 controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to detect VEGF -2578C/A, +460T/C, +1612G/A, +936C/T, and -634G/C polymorphisms. Compared with the control subjects, the RCC cancer cases were more likely to have a habit of cigarette smoking, and suffered from hypertension and diabetes. Conditional logistic regression analysis showed that individuals carrying the AA genotype of -2578C/A were more likely to greatly increase risk of RCC, and the CC genotype of +460T/C revealed a significant association with increased risk of RCC. The CA + AA genotype of -2578C/A had a significantly increased risk of RCC in ever cigarette smokers, and individuals who suffered from hypertension and diabetes. TC + CC genotype of +460T/C was significantly associated with the elevated risk of RCC in those suffered from hypertension and diabetes. Our study suggests that -2578C/A and +460T/C polymorphisms of VEGF modulate the risk of developing RCC in Chinese population.

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“…As functional SNPs in the VEGF gene can affect the expression of this protein in cancer cells, these SNPs can thus promote the angiogenic activity of tumors and accelerate the process of carcinogenesis (Ajaz et al, 2011;Sáenz-López et al, 2013). VEGF -634G/C is located in the 3'-untranslated region of the gene, and has been reported to have a role in influencing plasma VEGF levels (Stathopoulou et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Investigation of the role of VEGF gene polymorphisms in the risk of osteosarcoma

Zhang¹,

Bai²,

Zhang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We conducted a case-control study in a Chinese population, and assessed whether the VEGF -634G/C, +936C/T, and +1612G/A polymorphisms could affect the risk of osteosarcoma and its association with environmental factors. A total of 180 consecutive osteosarcoma patients and 360 controls were included in our study. The genotypes of VEGF -634G/C, +936C/T, and +1612G/A were determined by the polymerase chain reaction-restriction fragment length polymorphism assay. Conditional logistic regression analyses showed that subjects carrying the GG genotype and the G allele of VEGF -634G/C were significantly associated with increased risk of osteosarcoma compared to those with the CC genotype; the ORs (95%CIs) were 2.28 (1.31-3.96) and 1.51 (1.16-1.97) for the GG genotype and G allele, respectively. We found that the GG genotype of VEGF -634G/C was associated with a significantly increased risk 8284 G. Zhang et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 8283-8289 (2015) of osteosarcoma in patients of either gender with younger age and a family history of cancer. In summary, this study found that the VEGF -634G/C gene polymorphism was associated with an increased risk of osteosarcoma.

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A common variant highly associated with plasma VEGFA levels also contributes to the variation of both LDL-C and HDL-C

Cited by 30 publications

References 50 publications

Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study

Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study

Predictive value of vascular endothelial growth factor polymorphisms on the risk of renal cell carcinomas: a case–control study

Investigation of the role of VEGF gene polymorphisms in the risk of osteosarcoma

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