Combined effect of vascular endothelial growth factor and its receptor polymorphisms in endometriosis: a case-control study

Cardoso, Jéssica Vilarinho; Abrão, Maurício Simões; Vianna‐Jorge, Rosane; Ferrari, Renato; Berardo, Plínio Tostes; Machado, Daniel Escorsim; Perini, Jamila Alessandra

doi:10.1016/j.ejogrb.2016.10.046

Cited by 21 publications

(22 citation statements)

References 32 publications

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“…Women presenting previous diagnostic of adenomyosis, cancer, rheumatoid arthritis or hypertension-related chronic kidney disease where excluded from the study. All participants signed informed consent and their epidemiological, gynecological and clinical data were already published in our previous article [9].…”

Section: Methodsmentioning

confidence: 99%

“…As demonstrated in our previous study [9], endometriosis cases were divided into two groups according to the revised American Fertility Society classification: early stage (women with minimal or mild endometriosis - stage I and II, respectively; n = 109) and advanced stage (women with moderate or severe endometriosis - stage III and IV, respectively; n = 164). Besides, 10 participants had no information about the staging.…”

Section: Methodsmentioning

confidence: 99%

“…Even though endometriosis' etiology is not completely understood, there is strong evidence that angiogenesis is essential for the establishment and growth of endometriotic lesions [6], and genetic components can be involved in this process [7]. Our previous studies have demonstrated that polymorphisms in genes that regulates the angiogenic process, such as VEGF and KDR, can be involved in endometriosis risk [8,9]. Another important factor for the angiogenesis is the matrix metalloproteinases (MMPs) family, which consists of enzymes involved in extracellular matrix remodeling [10], allowing the angiogenic process.…”

Section: Introductionmentioning

confidence: 99%

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Matrix metalloproteinases 3 polymorphism increases the risk of developing advanced endometriosis and infertility: A case-control study

Cardoso

Machado

Silva

et al. 2019

European Journal of Obstetrics & Gynecology and Reproductiv

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Objective Endometriosis has a complex and multifactorial pathology, and it is considered one of the main causes of infertility nowadays. The angiogenic process, which involves remodeling of extracellular matrix, is crucial for the development of this disease, mainly by the action of the matrix metalloproteinase 3 (MMP-3). It is known that genetic factors can influence endometriosis, thus; we investigated the role of MMP3 276G>A polymorphism as a risk factor for the development of the disease and its symptoms. Study Design This case-control study included 283 women with endometriosis (cases) and 217 women without the disease (controls) who were submitted to laparoscopic or laparotomy surgery. Real-time polymerase chain reaction performed by TaqMan system was applied for all polymorphisms. A multivariate logistic regression was performed to evaluate the association between polymorphism and endometriosis or clinical and gynecological characteristics of the disease, using their respective odds ratios (OR) and 95% confidence intervals (CI). Results The allelic frequency of the MMP3 276 G > A polymorphism was 33.6% in controls and 40.3% in endometriosis cases. The allelic distribution was significantly different between the two ( P = 0.03). The variant genotype of MMP3 276AA was associated with increased endometriosis risk in the advanced endometriosis cases (OR: 2.08, 95% CI: 1.05 – 4.07 and OR: 1.87, 95% CI: 1.01 – 3.45). Regarding the symptoms, endometriosis-related infertile women had a positive association with the presence of MMP3 276 G > A polymorphism (OR: 3.13, 95% CI: 1.08–9.08 and OR: 3.30, 95% CI: 1.31 – 8.33). Conclusions These findings suggest that the MMP3 276A polymorphism is involved with advanced endometriosis cases and infertility, and these associations may implicate in the behavior of disease.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Matrix metalloproteinases 3 polymorphism increases the risk of developing advanced endometriosis and infertility: A case-control study

Cardoso

Machado

Silva

et al. 2019

European Journal of Obstetrics & Gynecology and Reproductiv

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“…However, these data have to be examined and evaluated with a critical eye, considering that the control group was recruited based on an ultrasound-based diagnosis only, negative for endometriosis and, as known, this method cannot exclude the occurrence of pelvic endometriosis. Moreover, Cardoso et al (41) conducted a study based on a Brazilian population and found that rs2305948 was also protective against the development of endometriosis, with this SNP also reducing cyclical urinary symptoms. VEGFR-2 is encoded by the KDR gene, located on chromosome 4q11-q12 and consists of 30 exons (27).…”

Section: Discussionmentioning

confidence: 99%

“…Considering that the pathogenesis of endometriosis is crucially dependent on angiogenesis that is signaled via VEGF and its receptor, VEGFR2, and taking into account various genetic associations detected between the rs2305948 SNP of VEGFR2 and endometriosis in different ethnic/racial populations (39)(40)(41), this study attempted to examine the potential genetic association between the rs2305948 (V297I) SNP and endometriosis in a homogeneous Greek population. This study also aimed to further elucidate the functional significance of this polymorphism by using a structural biological approach.…”

Section: Introductionmentioning

confidence: 99%

Implication of VEGFR2 in endometriosis: A structural biological and genetic approach

et al. 2019

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Vascular endothelial growth factor receptor 2 (VEGFR2) is a tyrosine kinase receptor, which exerts its activity by binding to VEGF, a major mediator of angiogenesis. Endometriosis is one of the most common gynecological diseases in women of reproductive age, characterized mainly by pelvic pain and infertility. Among the various hypotheses that have been suggested thus far for the development of this condition, it is considered that it is closely related to angiogenic responses. Polymorphisms of the VEGFR2 gene have already been shown to be associated with vascular diseases, such as coronary heart disease (CHD). In the present study, the authors sought to clarify the structural/functional consequences of rs2305948, a common single nucleotide polymorphism (SNP) of VEGFR2 in endometriosis and to investigate the association of this SNP with susceptibility to endometriosis, probably by influencing endothelial cells. This study comprised 162 patients with endometriosis (stages I-IV) hospitalized for endometriosis, diagnosed by laparoscopic intervention and histologically confirmed, and 170 women in the control group from a genetic homogeneous population. Genotyping of the V297I (rs2305948) polymorphism was performed through TaqMan technology. Three-dimensional (3D) homology modelling was applied for the localization of the polymorphism under study on the VEGFR2 protein. Modelling revealed that the V297I polymorphism may affect the efficiency of trans-autophosphorylation and cell signaling. The results of statistical analysis revealed that there was no significant allelic and genotypic association of the rs2305948 SNP between the disease (stages I-IV) and the control group. Further analysis did not reveal any association of this SNP with an increased susceptibility to endometriosis for stages I and II or III and IV of the disease only. Apart from structural data that suggest that the rs2305948 SNP of VEGFR2 gene may contribute to the pathogenesis of endometriosis by impairing VEGF signaling and increasing angiogenesis, in the present study, this SNP was not found to be associated with an increased susceptibility to endometriosis.

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The Role of the Microenvironment in Endometriosis: Parallels and Distinctions to Cancer

Rogers

2022

Biomarkers of the Tumor Microenvironment

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Combined effect of vascular endothelial growth factor and its receptor polymorphisms in endometriosis: a case-control study

Cited by 21 publications

References 32 publications

Matrix metalloproteinases 3 polymorphism increases the risk of developing advanced endometriosis and infertility: A case-control study

Matrix metalloproteinases 3 polymorphism increases the risk of developing advanced endometriosis and infertility: A case-control study

Implication of VEGFR2 in endometriosis: A structural biological and genetic approach

The Role of the Microenvironment in Endometriosis: Parallels and Distinctions to Cancer

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