Vascular endothelial growth factor (VEGF)-related single nucleotide polymorphisms rs10738760 and rs6921438 are not associated with diabetic retinopathy (DR) in Slovenian patients with type 2 diabetes mellitus (T2DM)

Terzić, Rifet; Cilenšek, Ines; Pleskovic, Ruda Zorc; Mankoč, Sara; Milutinović, Aleksandra

doi:10.17305/bjbms.2017.2068

Cited by 4 publications

(4 citation statements)

References 20 publications

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“…Similarly, they did not observe significant effects of rs6921438 or rs10738760 on diabetic microvascular complications in patients with T2DM [31]. In line with these and our findings are also the results of another study on Slovenian patients with T2DM [32], which reported no significant association between DR and rs6921438 and rs10738760 polymorphisms. Overall, the results from our and the previous studies indicate a more complex and perhaps indirect relationship between VEGF and T2DM and its microvascular complications, as suggested by Bonnefond et al [31].…”

Section: Discussionsupporting

confidence: 91%

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Vascular endothelial growth factor (VEGF)-related polymorphisms rs10738760 and rs6921438 are not risk factors for proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus (T2DM)

Sajovic

Cilenšek

Mankoč

et al. 2019

Bosn J of Basic Med Sci

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Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and has been investigated as a candidate gene in a number of conditions, including diabetes and its microvascular complications (e.g., retinopathy and nephropathy). Several VEGF-related polymorphisms have been shown to contribute to nearly half of the variability in circulating VEGF levels in healthy individuals. Our aim was to assess the association between VEGF-related rs10738760 and rs6921438 polymorphisms and proliferative diabetic retinopathy (PDR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated the effect of these polymorphisms on VEGF receptor 2 (VEGFR-2) expression in fibrovascular membranes (FVMs) from patients with PDR. This case-control study enrolled 505 unrelated patients with T2DM: 143 diabetic patients with PDR as a study group, and 362 patients with T2DM of >10 years duration and with no clinical signs of PDR as a control group. Patient clinical and laboratory data were obtained from their medical records. rs10738760 and rs6921438 polymorphisms were genotyped using TaqMan SNP Genotyping assay. VEGFR-2 expression was assessed by immunohistochemistry in 20 FVMs from patients with PDR, and numerical areal density of VEGFR-2-positive cells was calculated. The occurrence of PDR was 1.7 times higher in diabetic patients carrying GA genotype of rs6921438 compared to patients with GG genotype, with a borderline statistical significance (OR = 1.7, 95% CI = 1.00 -2.86, p = 0.05). In addition, A allele of rs6921438 was associated with increased VEGFR-2 expression in FVMs from PDR patients. However, we observed no association between AA genotype of rs6921438 nor between rs10738760 variants and PDR, indicating that the two polymorphisms are not genetic risk factors for PDR.

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Section: Discussionsupporting

confidence: 91%

“…Overall they reported no significant association between the two VEGF-related SNPs and the risk of T2DM, DN or DR [31]. Similarly, Terzić et al [32] showed that rs6921438 and rs10738760 were not associated with DR in Slovenian patients with T2DM.…”

Section: Introductionmentioning

confidence: 96%

Vascular endothelial growth factor (VEGF)-related polymorphisms rs10738760 and rs6921438 are not risk factors for proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus (T2DM)

Sajovic

Cilenšek

Mankoč

et al. 2019

Bosn J of Basic Med Sci

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“…Vascular endothelial growth factor (VEGF) is a crucial cytokine used to promote the formation of new blood vessels, which may promote vascular endothelial cells, smooth muscle cell mitosis, vascular permeability, and angiogenesis [9, 10]. Previous studies on the association between VEGF and vascular disease revealed that serum VEGF was significantly increased in patients with diabetes mellitus, and the increase of VEGF was closely associated with the germination of diabetic angiopathy [11, 12]. The present study intended to investigate the vascular lesion of type 2 diabetes mellitus in Goto-Kakizaki (GK) rats and human umbilical vein endothelial cells, in order to illustrate the mechanism of the pathogenesis of the vascular lesion of type 2 diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

To Explore the Pathogenesis of Vascular Lesion of Type 2 Diabetes Mellitus Based on the PI3K/Akt Signaling Pathway

Gao

Qin

Fang

et al. 2019

Journal of Diabetes Research

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Background. Type 2 diabetes mellitus (T2DM) has become a chronic disease, serious harm to human health. Complications of the blood pipe are the main cause of disability and death in diabetic patients, including vascular lesions that directly affects the prognosis of patients with diabetes and survival. This study was to determine the influence of high glucose and related mechanism of vascular lesion of type 2 diabetes mellitus pathogenesis. Methods. In vivo aorta abdominalis of GK rats was observed with blood pressure, heart rate, hematoxylin and eosin (H&E), Masson, and Verhoeff staining. In vitro cells were cultured with 30 mM glucose for 24 h. RT-QPCR was used to detect the mRNA expression of endothelial markers PTEN, PI3K, Akt, and VEGF. Immunofluorescence staining was used to detect the expression of PTEN, PI3K, Akt, and VEGF. PI3K and Akt phosphorylation levels were detected by Western blot analysis. Results. Heart rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure in the GK control group were higher compared with the Wistar control group and no difference compared with the GK experimental model group. Fluorescence intensity of VEGF, Akt, and PI3K in the high-sugar stimulus group was stronger than the control group; PTEN in the high-sugar stimulus group was weakening than the control group. VEGF, Akt, and PI3K mRNA in the high-sugar stimulus group were higher than the control group; protein expressions of VEGF, Akt, and PI3K in the high-sugar stimulus group were higher than the control group. PTEN mRNA in the high-sugar stimulus group was lower than the control group. Protein expression of PTEN in the high-sugar stimulus group was lower than the control group. Conclusions. Angiogenesis is an important pathogenesis of T2DM vascular disease, and PTEN plays a negative regulatory role in the development of new blood vessels and can inhibit the PI3K/Akt signaling pathway.

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“…This study could only find an association of rs13207351 with NPDR and rs5742632 with PDR [107]. Similarly, studies performed in the Caucasian Slovenian and Mexican PDR subjects did not observe an association between AA genotype of rs6921438 or rs10738760 [108,109] and rs3025021, rs3025035, rs2010963, respectively [110]; however, recent studies have also shown that rs2010963 is associated with the development and severity of DR in Egyptian [111] and Sudanese [112] patients.…”

Section: Vegf Genementioning

confidence: 57%

Genetics of Diabetic Retinopathy, a Leading Cause of Irreversible Blindness in the Industrialized World

Bhatwadekar

Shughoury

Belamkar

et al. 2021

Genes

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Diabetic retinopathy (DR) is a chronic complication of diabetes and a leading cause of blindness in the industrialized world. Traditional risk factors, such as glycemic control and duration of diabetes, are unable to explain why some individuals remain protected while others progress to a more severe form of the disease. Differences are also observed in DR heritability as well as the response to anti-vascular endothelial growth factor (VEGF) treatment. This review discusses various aspects of genetics in DR to shed light on DR pathogenesis and treatment. First, we discuss the global burden of DR followed by a discussion on disease pathogenesis as well as the role genetics plays in the prevalence and progression of DR. Subsequently, we provide a review of studies related to DR’s genetic contribution, such as candidate gene studies, linkage studies, and genome-wide association studies (GWAS) as well as other clinical and meta-analysis studies that have identified putative candidate genes. With the advent of newer cutting-edge technologies, identifying the genetic components in DR has played an important role in understanding DR incidence, progression, and response to treatment, thereby developing newer therapeutic targets and therapies.

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Vascular endothelial growth factor (VEGF)-related single nucleotide polymorphisms rs10738760 and rs6921438 are not associated with diabetic retinopathy (DR) in Slovenian patients with type 2 diabetes mellitus (T2DM)

Cited by 4 publications

References 20 publications

Vascular endothelial growth factor (VEGF)-related polymorphisms rs10738760 and rs6921438 are not risk factors for proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus (T2DM)

Vascular endothelial growth factor (VEGF)-related polymorphisms rs10738760 and rs6921438 are not risk factors for proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus (T2DM)

To Explore the Pathogenesis of Vascular Lesion of Type 2 Diabetes Mellitus Based on the PI3K/Akt Signaling Pathway

Genetics of Diabetic Retinopathy, a Leading Cause of Irreversible Blindness in the Industrialized World

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