VEGFA Rs699947 Research Articles

Polymorphism of angiogenesis regulation factor genes (VEGF/VEGFR), and extracellular matrix remodeling genes (MMP/TIMP), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema.

Cells of various organs and systems perform their functions and intercellular interactions not in an inert environment, but in the microenvironment of tissue fluids. Violations of the normal drainage of tissue fluids accompany lymphedema. An important mechanism of angiogenesis and vasculogenesis regulation in tissue fluids is the production and reception of vascular endothelial growth factors in combination with the regulation of matrix metalloproteinases. The aim of the work was to perform: a comparative analysis of some polymorphisms of vascular endothelial growth factor and their receptors and the genes encoding matrix metalloproteinases in two forms of lymphedema; an analysis of the relationship of these genes' polymorphisms with the levels of vascular endothelial growth factor and matrix metalloproteinases and their inhibitors in serum and affected tissues. Polymorphism of VEGF (rs699947, rs3025039), KDR (rs10020464, rs11133360), NRP2 (rs849530, rs849563, rs16837641), matrix metalloproteinases MMP2 (rs2438650), MMP3 (rs3025058), MMP9 (rs3918242), Timp1 (rs6609533) and their combinations were analyzed by the Restriction Fragment Length Polymorphism method and TaqMan RT-PCR. The serum and tissue fluid levels were determined using the ELISA test system. Changes in the frequency distribution of MMP2 genotypes in primary and MMP3 in secondary lymphedema are shown. Significant frequency differences in NRP2 genotypes were revealed by comparing primary and secondary lymphedema. Features of the distribution of complex genotypes in primary and secondary lymphedema were revealed. The correlation analysis revealed the interdependence of the concentrations of the MMP, TIMP and VEGF products and differences in the structure of the correlation matrices of patients with both forms of lymphedema. It was shown that, in primary lymphedema, genotypes associated with low MMP2 and TIMP2 in serum and tissue fluid are detected, while in secondary lymphedema, other associations of the production levels with combined genetic traits are observed.

Exudative Age-Related Macular Degeneration: Association between Treatment Efficacy and Single-Nucleotide Variants in RAD51B, TRIB1, COL8A1, COL10A1, IL-9, IL-10, and VEGFA Genes.

Age-related macular degeneration (AMD) is a progressive neurodegenerative condition leading to vision loss and eventual blindness, with exudative AMD posing a heightened risk due to choroidal neovascularization and localized edema. Therapies targeting the VEGF pathway aim to address this mechanism for treatment effectiveness. Our study aimed to evaluate associations between specific genetic variants (RAD51B rs8017304, rs2588809; TRIB1 rs6987702, rs4351379; COL8A1 rs13095226; COL10A1 rs1064583; IL-9 rs1859430, rs2069870, rs11741137, rs2069885, rs2069884; IL-10 rs1800871, rs1800872, rs1800896; VEGFA rs1570360, rs699947, rs3025033, rs2146323) and the response to anti-VEGF treatment for exudative AMD. We enrolled 119 patients with exudative AMD categorized as responders or non-responders based on their response to anti-VEGF treatment. Statistical analysis revealed that RAD51B rs8017304 heterozygous and homozygous minor allele carriers had increased CMT before treatment compared to wild-type genotype carriers (p = 0.004). Additionally, TRIB1 rs4351379 heterozygous and homozygous minor allele carriers exhibited a greater decrease in central macular thickness (CMT) after 6 months of treatment than wild-type genotype carriers (p = 0.030). IL-9 rs1859430, rs2069870, and rs2069884 heterozygous and homozygous minor allele carriers had worse BCVA before treatment than wild-type genotype carriers (p = 0.018, p = 0.012, p = 0.041, respectively). Conversely, IL-9 rs2069885 heterozygous and homozygous minor allele carriers showed greater improvement in BCVA after 6 months compared to wild-type genotype carriers (p = 0.032). Furthermore, VEGFA rs699947 heterozygous and homozygous minor allele carriers had better BCVA before treatment and after 3 and 6 months of treatment than wild-type genotype carriers (p = 0.003, p = 0.022, respectively), with these carriers also exhibiting higher CMT after 6 months of anti-VEGF treatment (p = 0.032). Not all results remained statistically significant under this stringent correction for multiple comparisons. The comparisons of the serum concentrations of IL-10, VEGF-A, and VEGF-R2/KDR between non-responders and responders did not yield statistically significant differences. Our study identified significant associations between genetic variants, including RAD51B rs8017304, TRIB1 rs4351379, IL-9 rs1859430, rs2069870, rs2069884, rs2069885, and VEGFA rs699947, and parameters related to the efficacy of exudative AMD treatment, such as BCVA and CMT.

Association of the Complement Factor H Y402H Polymorphism and Response to Anti-Vascular Endothelial Growth Factor Treatment in Age-Related Macular Degeneration: An Updated Meta-Analysis.

Anti-vascular endothelial growth factor (anti-VEGF) agents have a variable effect on patients with age-related macular degeneration (AMD) that has been attributed to several causes, including genetic factors. We evaluated the effects of Complement Factor H (CFH) rs1061170/Y402H polymorphism on the response to anti-VEGF therapy among AMD patients. PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were used for a literature search. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated to assess the effects of CFH Y402H polymorphism on the response to anti-VEGF therapy in AMD. I2 was used to present the amount of heterogeneity. We used STATA version 14.0 software. Twenty-five papers reporting data for 4,681 patients were included in this study. Better response to anti-VEGF therapy was seen in T over C (OR = 1.25, 95% CI = 1.04-1.50), TT over CC (OR = 1.60, 95% CI = 1.06-2.4), and TT + TC over CC (OR = 1.68, 95% CI = 1.23-2.28) genotypes. There was no significant difference in the three other genetic models (TT vs. TC, TT vs. TC + CC, TC vs. TT + CC). In Asians, no significant difference was observed in all six genetic models. Ranibizumab and bevacizumab had similar efficacy; however, conbercept was more effective in homozygous genotypes. The literature indicated that TT and TC genotypes and T allele were associated with a better functional response, while the CC genotype and C alleles had a better anatomical response. The combination of risk alleles in ARMS2 A69S (rs10490924), VEGF-A (rs699947), and VEGF-A (rs833069) with Y420H is a predictor of non-respondents. In patients with AMD, the CFH Y402H is a predictor of the response to anti-VEGF agents and should be considered in the treatment plan.

Genetic Biomarkers of Sorafenib Response in Patients with Hepatocellular Carcinoma.

The identification of biomarkers for predicting inter-individual sorafenib response variability could allow hepatocellular carcinoma (HCC) patient stratification. SNPs in angiogenesis- and drug absorption, distribution, metabolism, and excretion (ADME)-related genes were evaluated to identify new potential predictive biomarkers of sorafenib response in HCC patients. Five known SNPs in angiogenesis-related genes, including VEGF-A, VEGF-C, HIF-1a, ANGPT2, and NOS3, were investigated in 34 HCC patients (9 sorafenib responders and 25 non-responders). A subgroup of 23 patients was genotyped for SNPs in ADME genes. A machine learning classifier method was used to discover classification rules for our dataset. We found that only the VEGF-A (rs2010963) C allele and CC genotype were significantly associated with sorafenib response. ADME-related gene analysis identified 10 polymorphic variants in ADH1A (rs6811453), ADH6 (rs10008281), SULT1A2/CCDC101 (rs11401), CYP26A1 (rs7905939), DPYD (rs2297595 and rs1801265), FMO2 (rs2020863), and SLC22A14 (rs149738, rs171248, and rs183574) significantly associated with sorafenib response. We have identified a genetic signature of predictive response that could permit non-responder/responder patient stratification. Angiogenesis- and ADME-related genes correlation was confirmed by cumulative genetic risk score and network and pathway enrichment analysis. Our findings provide a proof of concept that needs further validation in follow-up studies for HCC patient stratification for sorafenib prescription.

Genetic predictors of abdominal complications after cardiac surgery: a prospective study

Introduction: The prediction of postoperative abdominal complications is a continuing concern in the cardiac surgery. Identifying genetic predictors will allow a better understanding of the pathophysiological mechanisms underlying postoperative disorders and their prevention.Objective: To identify genetic predictors of abdominal complications after heart surgery.Methods: A prospective study was carried out at the Federal Center for Cardiovascular Surgery (Chelyabinsk) involving 72 patients with abdominal complications and 102 controls without such complications. The distribution of genotypes was assessed for adherence to the Hardy-Weinberg distribution using the exact method according to the SNP-HWE algorithm in the PLINK package (version 1.9). To identify marker genes associated with the risk of abdominal complications, 6 models were evaluated for each polymorphic gene: allelic, codominant, dominant, recessive, overdominant, and log-additive. To analyze the SNPs of the IL6 (rs1800795), TNF (rs1800629), and SERPINE1 (rs1799768) genes, real-time polymerase chain reaction (PCR) was performed on a Rotor-Gene 6000 detecting cycler (Corbett Research Pty Ltd., Mortlake, Australia) using primers and probes manufactured by Syntol CJSC (Moscow, Russia) according to the manufacturer's instructions. To analyze the SNPs of the IL1B (rs1143634), CXCL8 (rs4073), IL10 (rs1800872), APOE (rs429358), FABP2 (rs1799883), NOS3 (rs1799983), VEGFA (rs699947) genes, real-time PCR was performed on a DTprime 4 analyzer (DNA-Technology, Moscow, Russia) using primers and probes manufactured by TestGene LLC (Ulyanovsk, Russia) according to the manufacturer's instructions. The determination of the SNP of the TLR3 gene (rs3775291) relied on real-time PCR according to melting curves using TestGene LLC reagent kits on a DTprime 4 device.Results: Two genes, IL1B rs1143634 and FABP2 rs1799883, were found to be associated with the risk of abdominal complications. Following the adjustment for multiple comparisons, only FABP2 rs1799883 remained statistically significant. The rs1799883 polymorphism of the FABP2 gene can be considered a predictor of the risk of abdominal complications and can be evaluated within the codominant and dominant models, which exhibit similar p-values (0.003 and 0.002, respectively). Overall, the analysis of the obtained data suggests that the risk of abdominal complications is associated with the presence of the mutant allele C in the genome, likely due to its dominance. Specifically, in the dominant model, the odds ratio was 3.53 (95% CI 1.62 to 7.70).Conclusion: The most significant markers of the risk of abdominal complications were the IL1B (rs1143634) and FABP2 (rs1799883) genes, of which FABP2 (rs1799883) remained statistically significant after adjusting for multiple comparisons. Its polymorphism as a predictor of abdominal complications can be evaluated within the codominant and dominant models. Received 13 June 2023. Revised 28 November 2023. Accepted 29 November 2023. Funding: The study was supported by the Russian Science Foundation, project No. 22-25-20016, https://rscf.ru/project/22-25-20016/ Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: O.S. Abramovskikh, A.A. Fokin, D.V. BelovData collection and analysis: Yu.V. LoginovaStatistical analysis: M.A. ZotovaDrafting the article: D.V. BelovCritical revision of the article: Yu.V. LoginovaFinal approval of the version to be published: D.V. Belov, O.S. Abramovskikh, M.A. Zotova, Yu.V. Loginova, A.A. Fokin

Application of PCR-RFLP technique for determining the VEGFA rs3025039 (+936C>T) polymorphism

Background: The VEGFA gene encodes vascular endothelial growth factor A (VEGF-A), which plays a key role in vasculogenesis and angiogenesis. The VEGFA rs3025039 (+936C>T) polymorphism is associated with many diseases. This study aimed to: (1) Apply PCR-RFLP technique to identify the VEGFA rs3025039 (+936C>T) polymorphism; (2) Primarily evaluate the distribution of genotypes and allele frequencies of the rs3025039 polymorphism in volunteers. Materials and methods: DNA extraction was isolated from peripheral blood of 60 volunteers. Determining the VEGFA rs3025039 (+936C>T) polymorphism by PCR-RFLP technique. Confirming the results of the genotypes randomly by Sanger sequencing. Results: All PCR-RFLP results of validated samples were in concordance with sequencing results. The distribution of CC, CT and TT genotypes by rs3025039 polymorphism accounted for 80%, 16.7% and 3.3%, respectively. The frequencies of C and T alleles were 88.3% and 11.7%, respectively. Conclusion: Successfully applying PCR-RFLP technique to determine the VEGFA rs3025039 (+936C>T) polymorphism, which establishes the groundwork for further research into the association between this polymorphism and various disorders. Key words: VEGFA, rs3025039, PCR-RFLP.

Vascular Endothelial Growth Factor A serum levels and common gene polymorphisms in generalized periodontitis affected patients

Objective To evaluate and compare the associations of VEGFA serum levels and SNPs (rs1570360, rs699947, rs3025033, and rs2146323) with periodontitis in study participants grouped by gender. Methods The study enrolled 261 patients with periodontitis and 441 healthy controls as a reference group. Patients underwent periodontal examination and radiographic analysis to confirm the periodontitis diagnosis. Blood samples were collected, and the DNA salting-out method was used for DNA extraction from peripheral venous blood. Genotyping of VEGFA (rs1570360, rs699947, rs3025033, and rs2146323) was performed using real-time polymerase chain reaction (RT-PCR) and serum level analysis was done for 80 individuals − 40 periodontitis-affected patients and 40 reference group subjects. Results The analysis of VEGFA (rs1570360, rs699947, rs3025033, and rs2146323) showed that the rs3025033 GG genotype was less frequent in the periodontitis group than in the reference group (1.6% vs. 5.7%,p = 0.008). VEGFA serum levels were not statistically significantly different between periodontitis patients and reference group subjects (554.29 (522.38) ng/ml vs. 581.32 (348.16) ng/ml, p = 0.786). Individuals carrying rs1570360, rs699947, rs3025033, and rs2146323 haplotype A-A-G-A had decreased risks of periodontitis, while rare haplotype of VEGFA (rs1570360, rs699947, rs3025033, and rs2146323) was associated with increased odds of periodontitis (OR= 0.42; 95% CI: 0.20–0.85; p < 0.017; OR= 4.08; 95% CI: 1.86–8.94; p < 0.0001, respectively). Conclusion The rs3025033 GG genotype and the rs1570360, rs699947, rs3025033, and rs2146323 A-A-G-A haplotypes may play a protective role in the development of periodontitis, but a less common haplotype of the same VEGFA polymorphism may be associated with the risk of developing periodontitis.

Investigation of VEGF (rs 699947) polymorphism in the progression of Rheumatoid Arthritis (RA) and in-silico nanoparticle drug delivery of potential phytochemicals to cure RA.

Mutation in the VEGF gene disturbs the production of chondrocytes and angiogenesis which are essential for cartilage health. Cytokines and chemokines produced by auto-activation of B-cells degrade cartilage. Bruton's Tyrosine Kinase (BTK) plays a crucial role in the activation of these B-cells. VEGF has a central part in angiogenesis, in the recruitment of endothelial cells, and is involved in mechanisms that result in tumour formation. The objective of this research is to investigate the potential role of VEGF polymorphism in the development of Rheumatoid Arthritis (RA) and the screening of potential natural, synthetic BTK inhibitor compounds as possible in-silico chemotherapeutic agents to control auto-activation of B-cells and cartilage degrading cytokines. In this study, it had been shown that allele A frequency was significantly higher than that of allele C in RA-positive patients as compared to controls. Hence it depicts that allele A of VEGF (rs699947) can increase the risk of RA while allele C has a protective role. The phytochemicals which showed maximum binding affinity at the inhibitory site of BTK include beta boswellic acid, tanshinone, and baicalin. These phytochemicals as BTK inhibitor give insights to use them as anti-arthritic compounds by nanoparticle drug delivery mechanism.

Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease

There is increasing evidence for the involvement of blood–brain barrier (BBB) in vascular dementia (VaD) and Alzheimer´s disease (AD) pathogenesis. However, the role of endothelial function-related genes in these disorders remains unclear. We evaluated the association of four single-nucleotide polymorphisms (VEGF, VEGFR2 and NOS3) with diagnosis and rate of cognitive decline in AD and VaD in a Spanish case–control cohort (150 VaD, 147 AD and 150 controls). Participants carrying -604AA genotype in VEGFR2 (rs2071559) were less susceptible to VaD after multiple testing. Further analysis for VaD subtype revealed a significant difference between small-vessel VaD patients and controls, but not for large-vessel VaD patients. In addition, -2578A and -460C alleles in VEGF (rs699947 and rs833061) showed to decrease the risk of AD, whereas NOS3 (rs1799983) influenced disease progression. Our study supports previous findings of a deleterious effect of VEGFR2 reduced expression on small-vessel disease, but not on large-vessel disease; as well as a detrimental effect of down-regulating VEGF and eNOS in AD, affecting vascular permeability and neuronal survival. These data highlight the relevance of endothelial function and, therefore, BBB in both VaD and AD.

VEGFA rs3025039 is associated with phenotype severity of myelofibrosis-type megakaryocyte dysplasia.

VEGFA rs3025039 is associated with phenotype severity of myelofibrosis-type megakaryocyte dysplasia.

Hypoxia-Inducible Pathway Polymorphisms and Their Role in the Complications of Prematurity.

Excessive oxidative stress resulting from hyperoxia or hypoxia is a recognized risk factor for diseases of prematurity. However, the role of the hypoxia-related pathway in the development of these diseases has not been well studied. Therefore, this study aimed to investigate the association between four functional single nucleotide polymorphisms (SNPs) in the hypoxia-related pathway, and the development of complications of prematurity in relation to perinatal hypoxia. A total of 334 newborns born before or on the 32nd week of gestation were included in the study. The SNPs studied were HIF1A rs11549465 and rs11549467, VEGFA rs2010963, and rs833061. The findings suggest that the HIF1A rs11549465T allele is an independent protective factor against necrotizing enterocolitis (NEC), but may increase the risk of diffuse white matter injury (DWMI) in newborns exposed to hypoxia at birth and long-term oxygen supplementation. In addition, the rs11549467A allele was found to be an independent protective factor against respiratory distress syndrome (RDS). No significant associations with VEGFA SNPs were observed. These findings indicate the potential involvement of the hypoxia-inducible pathway in the pathogenesis of complications of prematurity. Studies with larger sample sizes are needed to confirm these results and explore their clinical implications.

Prognostic impact of serum vascular endothelial growth factor and VEGF gene polymorphism (rs2010963) in breast cancer patients

Back groundVascular Endothelial Growth Factor (VEGF) mediates breast carcinogenesis. Several studies shown that, VEGF is associated with increased breast cancer risk. However its prognostic significance and expression in different molecular subtypes remain unclear. The current study aimed to evaluate the diagnostic and prognostic role of serum VEGF and VEGF rs2010963 polymorphism in Egyptian women with breast cancer. AimThe current study aimed to evaluate the diagnostic and prognostic role of serum VEGF and VEGF rs2010963 polymorphism in Egyptian women with breast cancer. Subjects and methodsThis study was held in Menoufia University Hospital and included 275 participants, 150 women with invasive breast cancer and 125 women as healthy controls. Serum VEGF was assayed by ELISA technique and genotyping of VEGF rs2010963 polymorphism was analyzed by real time PCR. ResultsThe frequency of GG, CG genotypes and G allele were higher in breast cancer group when compared to the control group (p value = 0.001). In breast cancer patients there was significant relation between VEGF gene (C/G) polymorphism and patient age, tumor and nodal stage, molecular subtype and higher level of serum of CA15–3, CEA and VEGF for patients with GG genotype (P ≤ 0.05). Multivariate Cox regression analysis of factors affecting survival showed that advanced tumor stage, presence of metastasis, serum level of VEGF and GG rs 2010963VEGF gene polymorphism were independent factors affecting patient survival (P ≤ 0.05). Conclusionrs2010963 VEGF gene polymorphism and serum VEGF could be considered as potential risk factors for breast cancer, Patients with breast cancer presenting the GG genotype have the highest serum VEGF levels, large tumor size, advanced tumor stage and shorter survival than CC carriers.

Endothelial nitric oxide synthase rs1799983 gene polymorphism is associated with the risk of developing intracranial aneurysm.

The intracranial aneurysm (IA) rupture is associated with a subarachnoid hemorrhage. One third of patients die, and one third remain depend for daily activities. Genetic factors are crucial in the formation and clinical evolution of IAs. Multiple loci have been associated with AIs, much of them implicating multiple pathways related to vascular endothelial maintenance and extracellular matrix integrity. Thus, the aim of our study was to characterize whether polymorphisms in genes implicated in the vascular endothelial maintenance could modify the risk of developing IAs. We have studied 176 patients with IA recruited in the Service of Neurosurgery at the University Hospital of Valladolid (Spain) and a control group if 150 sex-matched healthy subjects. Clinical variables were collected from each patient. We have analyzed VEGFA rs833061, VEGFR2 rs2071559, endothelin rs5370, endoglin rs3739817, and eNOS rs1799983 polymorphisms. Our results showed that allele T of the eNOS rs1799983 polymorphism is correlated with decreased risk of developing the disease; thus, allele G of the eNOS rs1799983 polymorphism increased the risk of developing IA. The association of eNOS rs1799983 polymorphism with the risk to suffer IA reinforces the hypothesis that genetic variants in eNOS gene could be crucial in the pathogenesis of IA.

Association of &lt;i&gt;VEGF&lt;/i&gt; gene rs699947 and rs2010963 polymorphisms with vascular endothelial growth factor levels in the blood serum of children with lupus nephritis

The growth factor genes VEGF and TGFB1 are involved in the normal functioning of the kidneys, and some polymorphic loci of these genes determine a genetic predisposition to the autoimmune diseases, including systemic lupus erythematosus (SLE) and its dangerous complication, lupus nephritis (LN). The products of these genes, in particular, the vascular endothelial growth factor protein and the transforming growth factor β1 protein are used in clinical practice as markers of endothelial dysfunction for early diagnosis of kidney pathology. However, the relationship between the expression of these proteins and the genotypes/alleles of the polymorphic loci of these genes has not been studied enough, which requires clarification of this issue for the child population of Belarus. In this work, we analyzed the associations of the TGFB1 (rs1800469) and VEGF (rs699947 and rs2010963) gene genotypes with the concentration of their products in the blood serum of patients with LN during exacerbation and remission of the disease. The study did not find a significant relationship between polymorphic variants of the TGFB1 gene (rs1800469) and levels of its product in the blood. An association has been established between the rs699947 and rs2010963 polymorphic variants of the VEGF gene and the serum concentration of the gene product in pediatric patients with LN during exacerbation. It was found that the homozygous minor genotype AA of the polymorphic locus rs699947 and the group of genotypes GC + CC containing at least one minor allele of the locus rs2010963 are associated with higher levels of the gene product in the blood serum of children with LN during disease exacerbation (p &lt; 0.001 and p = 0.036, respectively). Thus, VEGF polymorphic variants associated with an increased concentration of the gene product in the blood serum during disease exacerbation can be considered as markers of the risk of disease exacerbation in patients with LN.

Gene polymorphisms and prognosis of head and neck squamous cell carcinoma: a systematic review.

Head and neck squamous cell carcinomas (HNSCCs) are associated with variable prognosis even with similar clinical characteristics and treatments. Gene polymorphisms have been suggested as prognostic factors for HNSCC which can justified this variable prognosis. So, the aim was to review literatures on gene polymorphisms and prognosis of HNSCCs. A systematic search was conducted using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases to find all related articles published up to December 2021 in the field of gene polymorphisms and HNSCC prognosis. Of 1029 initial searched articles, 71 articles were selected for inclusion in this systematic review. About 93 genes and 204 polymorphisms have been discussed in these articles. Among the most studied polymorphisms, the XRCC1 Arg399Gln and Arg194Trp polymorphisms were not associated with survival in most studies; the ERCC1 C19007T polymorphism had no significant association in any of the studies. Different gene polymorphisms of glutathione s-transferase family, including GSTM1 deletion, GSTT1 deletion and GSTP1 A313G, were not associated with survival in included studies. There are conflicting results regarding the association between polymorphisms such as ERCC2 A35931C, Asp312Asn, ERCC5 rs1047768 and rs17655 with HNSCC prognosis. Less studied polymorphisms, such as hOGG1 rs1052133 or the VEGF rs699947, were generally not associated with HNSCC prognosis. Reviewed articles reported varied and contradictory results regarding the association of gene polymorphisms and HNSCC prognosis, which necessitates further studies along with meta-analysis on the results of such studies.

Diabetic retinopathy progression associated with haplotypes of two VEGFA SNPs rs2010963 and rs699947

ABSTRACT Diabetes-related retinopathy (DR) is one of the sight-threatening diseases. The present case–control study screened 134 patients with type 2 diabetes and 36 healthy ones without diabetes. The genotyping of SNPs rs2010963 and rs699947 of the VEGF gene were done by tetra primers ARMS-PCR. The mutant GG genotype of rs2010963 was significantly associated with DR (OR = 10.29; 95% CI = 2.20–59.06; p = 0.004). No significant associations existed between patients with DR and those with NDR or controls in the genotype or allele frequencies of rs699947 polymorphism. The haplotype analysis for rs2010963 and rs699947 shows the CG haplotype was significantly different between DR and NDR OR 2.0 (95% CI:1.02–3.93), p = 0.043. and between DR and control OR 2.42 (95% CI: 1.2–4.65), p = 0.0108‎. The two SNPs showed moderate Linkage disequilibrium (LD) ‎between DR and control, D’ = 0.64 also, moderate LD between DR cases and NDR, D’ = 0.75. No significant importance for rs699947 SNP with diabetic retinopathy. The 2010963 SNP in the VEGF gene is associated with the risk of NPDR and PDR. The findings also suggest a moderate LD in the two SNPs and their CG haplotype associated with DR progression.

Genetic Predictors of Development of Diabetic Foot Syndrome in Patients with Diabetes Mellitus

An increase in the population of patients with diabetes mellitus affects the incidence of diabetic foot syndrome (DFS), as its chronic complication. Among the various types of growth factors that play a role in the development of late complications of diabetes, vascular endothelial growth factor, VEGF, is currently in the focus of attention. The study conducted by the authors was aimed at determining the relationship between the G634C polymorphism of the VEGFA rs2010963 gene and the predisposition to the development of diabetic foot syndrome in patients with diabetes mellitus. We examined 96 patients aged 39 to 76 years with diabetes mellitus complicated by diabetic foot syndrome. Based on the studies, it was determined that the G634C polymorphism in the VEGFA gene (rs2010963) is involved in the formation and development of diabetic foot syndrome in patients with diabetes mellitus.

Clonal Megakaryocyte Dysplasia with Isolated Thrombocytosis Is a Distinct Myeloproliferative Neoplasm Phenotype

Introduction: About 15% of people with a myeloproliferative neoplasm (MPN) are identified as MPN, unclassifiable using the 2016 WHO classification. Methods: We tested whether persons with platelet concentration ≥450 × 10E+9/L, bone marrow megakaryocyte morphology typical of prefibrotic/early myelofibrosis (pre-MF), and no minor criteria of pre-MF should be classified as a distinct MPN subtype, clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT). Results: 139 subjects meet these criteria who we compared with primary myelofibrosis (PMF) including 402 with pre-MF and 521 with overt myelofibrosis. CMD-IT subjects were more likely female and younger. They had lower frequencies of JAK2^V617F compared with persons with PMF (55% vs. 70%; p < 0.001) and higher frequencies of CALR mutations (37% vs. 17%; p < 0.001). They also had lower frequency of variations associated with JAK2^V617F susceptibility, JAK2 46/1 (35% vs. 47%; p = 0.021), and VEGFA rs3025039 (12% vs. 17%; p = 0.030). Subjects with CMD-IT had lower incidences of thrombotic events compared with those with pre-MF (9.7% vs. 26%; p < 0.001) and longer survival (median, not reached vs. 23 years; HR = 0.34 (0.10, 0.30); p < 0.001). Conclusion: Our data indicate CMD-IT is a distinct MPN subtype and should be included in the classification of myeloid neoplasms.

DNA Polymorphisms in Pregnant Women with Sticky Platelet Syndrome.

Sticky platelet syndrome (SPS) is a thrombophilia caused by the increased aggregability of platelets in response to the addition of low concentrations of epinephrine (EPI) and/or adenosine diphosphate (ADP). Some of the single nucleotide polymorphisms (SNP), alleles and haplotypes of platelet glycoprotein receptors were proved to have a role in the etiology of thrombotic episodes When comparing SPS and the control group, in VEGFA rs3025039, the p value for both CC vs. TT and CT vs. TT analyses was &lt;0.001. Interestingly, no minor TT genotype was present in the SPS group, suggesting the thrombotic pathogenesis of recurrent spontaneous abortions (RSA) in these patients. Moreover, we found a significant difference in the presence of AT containing a risky A allele and TT genotype of ALPP rs13026692 (p = 0.034) in SPS patients when compared with the controls. Additionally, we detected a decreased frequency of the GG (CC) genotype of FOXP3 rs3761548 in patients with SPS and RSA when compared with the control group (p value for the CC (GG) vs. AA (TT) 0.021). This might indicate an evolutionary protective mechanism of the A (T) allele in the SPS group against thrombotic complications in pregnancy. These results can be used for antithrombotic management in such pregnant patients.

VEGFA rs2010963 GG genotype is associated with superior adaptations to resistance versus endurance training in the same group of healthy, young men

PurposeWe used a within-subject, cross-over study to determine the relationship between the intra-individual adaptations to four weeks’ resistance (RT) versus four weeks’ endurance (END) training, and we investigated whether three single nucleotide polymorphisms (SNPs) were associated with these adaptations.MethodsThirty untrained, healthy, young men completed a cycling test to exhaustion to determine peak oxygen uptake (V̇O2peak), and a knee extension (KE) maximum voluntary isometric contraction (MVIC) of the right leg before and after four weeks’ supervised RT (four sets of 10 repetitions at 80% single repetition maximum unilateral KE exercise, three times weekly) and four weeks’ supervised END (30 min combined continuous/interval cycling, three times weekly), separated by a three-week washout phase. Participants were genotyped for the ACTN3 rs1815739, NOS3 rs2070744 and VEGFA rs2010963 SNPs.ResultsThe intra-individual adaptations regarding percentage changes in MVIC force and V̇O2peak following RT and END, respectively, were unrelated (r2 = 0.003; P = 0.79). However, a VEGFA genotype × training modality interaction (P = 0.007) demonstrated that VEGFA GG homozygotes increased their MVIC force after RT (+ 20.9 ± 13.2%) more than they increased their V̇O2peak after END (+ 8.4 ± 9.1%, P = 0.005), and more than VEGFA C-allele carriers increased their MVIC force after RT (+ 12.2 ± 8.1%, P = 0.04). There were no genotype × training modality interactions for the ACTN3 or NOS3 SNPs.ConclusionHigh/low responders to RT were not consequently high/low responders to END or vice versa. However, preferential adaptation of VEGFA rs2010963 GG homozygotes to RT over END, and their greater adaptation to RT compared to VEGFA C-allele carriers, indicate a novel genetic predisposition for superior RT adaptation.