Dataset Information

The association between vascular endothelial growth factor (VEGF) +405G>C genetic polymorphism and endometriosis.

ABSTRACT: The vascular endothelial growth factor (VEGF) is one of the most important candidate genes for the development of endometriosis, and VEGF genetic polymorphisms might be potentially associated with endometriosis risk. However, the results still remain controversial. The objective of this study aimed to perform a comprehensive meta-analysis to explore a better understanding of the effects of VEGF +405G>C genetic polymorphism on the risk of endometriosis. A total of eleven eligible studies were eventually identified in this meta-analysis, including 2829 endometriosis cases and 2947 controls. In the overall analysis, no significant association between the VEGF +405G>C genetic polymorphism and the risk of endometriosis was detected in all genetic models (for homozygote comparison [CC versus vs. GG]: OR?=?1.21, 95% CI 0.67-2.19, P?=?0.537; for heterozygote comparison [CG vs. GG]: OR?=?1.16, 95% CI 0.86-1.56, P?=?0.348; for dominant comparison CC/CG vs. GG: OR?=?1.10, 95% CI 0.93-1.30, P?=?0.263; for recessive comparison [CC vs. CG/GG]: OR?=?1.03, 95% CI 0.73-1.47, P?=?0.857; allele comparison [C vs. G]: OR?=?0.99, 95% CI 0.70-1.40, P?=?0.962). In the subgroup analysis by ethnicities, there was no significant association between VEGF +405G>C genetic polymorphism and endometriosis risk in Asians and/or Caucasians under all genetic models (all P-values?>0.05). No publication bias was observed in this study. This meta-analysis supports that the VEGF +405G>C genetic polymorphism is not significant associated with the risk of endometriosis.

SUBMITTER: Fang F

PROVIDER: S-EPMC4935365 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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The association between vascular endothelial growth factor (VEGF) +405G>C genetic polymorphism and endometriosis.

Fang Fang F Gong Lili L Wang Xiaojuan X Zhang Ling L

Experimental biology and medicine (Maywood, N.J.) 20150107 9

The vascular endothelial growth factor (VEGF) is one of the most important candidate genes for the development of endometriosis, and VEGF genetic polymorphisms might be potentially associated with endometriosis risk. However, the results still remain controversial. The objective of this study aimed to perform a comprehensive meta-analysis to explore a better understanding of the effects of VEGF +405G>C genetic polymorphism on the risk of endometriosis. A total of eleven eligible studies were eve ...[more]

PMID: 25573961

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Project description:Rheumatoid arthritis (RA), is marked by joint inflammation leading to pannus formation which results in cartilage destruction promoting bone erosion. The pathological hallmark of RA includes synovial hyperplasia and synovial angiogenesis. Active tissue neovascularization is observed in RA. Vascular endothelial Growth factor A (VEGFA), an endothelial cell-specific proangiogenic molecule is triggered by hypoxic cells and its levels are upregulated in RA. The aim of this study was to investigate functional and pathogenic VEGFA variants and to identify the impact of point mutation in VEGFA's interaction with VEGFR2 and how these polymorphisms affect the susceptibility and severity of RA. We investigated impact of these point mutations on the stability of VEGFA using various computational tools. These mutations were further identified by conservational profile as they are highly involved as structural and functional mutations. Furthermore, these selected variants were modelled and docked against targeted domain regions IGD2 and IGD3 of VEGFR2. Further molecular dynamic simulations were performed using Gromacs. Out of 168 nsSNPS, 19 were highlighted as highly pathogenic using insilico prediction tools. InterPro and ConSurf revealed domains and conserved variants respectively. After stability analysis, we concluded that almost all the mutations were responsible for decreasing the protein stability. HOPE predicted that all the selected damaging nsSNPs were present in the domain which is essential for the functioning of VEGFA protein. Constructed Ramachandran plot and ERRAT validated the quality of all the models. Based on the interactions predicted by STRING database, we performed Protein-Protein docking between VEGFA and VEGFR2. We found few conserved interactions and new polar contacts among wild-type and mutants with VEGFR2. From the simulations, we concluded that mutant R108Q was the most stabilizing mutant among all others whereas R82Q, C86Y, and R108W complexed with VEGFR2 were comparatively less stabilizing as compared to the wild type. This study provides insight into pathogenic nsSNPs that can affect VEGFA protein structure and function. These high-risk variants must be taken into consideration for genetic screening of patients suffering from RA.

Project description:BACKGROUND: Endometriosis is regarded as a complex and heterogeneous disease in which genetic and environmental factors contribute to the phenotype. The Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of endometriosis. The present study was aimed at investigating the contribution of VEGF polymorphisms as risk factors for the development of endometriosis. This is the first study to evaluate the combined influence of the five most common VEGF polymorphisms. METHODS: This study was conducted at two hospitals from the Brazilian public health system, and comprised 294 women submitted to laparoscopic or laparotomy surgery: 182 patients had a histologically confirmed diagnosis of endometriosis (cases), whereas 112 had no evidence of the disease (controls). The VEGF polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model. RESULTS: Endometriosis patients and controls did not differ regarding age distribution, whereas the body mass index was significantly lower in endometriosis patients, when compared with controls (23.1?±?3.9 versus 27.3?±?5.9, P?<?0.001). The evaluation of gynecological symptoms, including dysmenorrhea, non-cyclic chronic pelvic pain, dyspareunia and infertility, indicates significantly higher prevalences among endometriosis cases. The variant allele -1154A was significantly associated with endometriosis, either considering all cases (OR: 1.90, 95% CI: 1.23-2.97), deep infiltrating endometriosis (DIE) (OR: 1.83, 95% CI: 1.16-2.90) or moderate and severe endometriosis (stages III-IV) (OR: 1.97, 95% CI: 1.21-3.19). No significant differences were found in allele or genotype distributions of the -2578C?>?A, -460 T?>?C, +405G?>?C and +936C?>?T polymorphisms between endometriosis cases and controls. A total of six haplotypes were inferred derived from four polymorphisms (-2578C?>?A, -460 T?>?C, -1154G?>?A and +405G?>?C). There was a protective association between CCGG haplotype and endometriosis, either considering all cases (OR: 0.36, 95% CI: 0.15-0.86), DIE (OR: 0.37 95% CI: 0.15 - 0.90) or stages III-IV (OR: 0.35 95% CI: 0.13 - 0.95). CONCLUSIONS: The present results indicate a positive association between VEGF -1154G?>?A and the risk of developing endometriosis, whereas the CCGG haplotype may be protective against the development of disease.

Dataset Information

The association between vascular endothelial growth factor (VEGF) +405G>C genetic polymorphism and endometriosis.

Publications

The association between vascular endothelial growth factor (VEGF) +405G>C genetic polymorphism and endometriosis.

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