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

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• 作者：Jé ; ssica Vilarinho Cardoso^a ; ^b ; Maurí ; cio Simõ ; es Abrã ; o^c ; Rosane Vianna-Jorge^a ; ^d ; Renato Ferrari^e ; Plí ; nio Tostes Berardo^f ; Daniel Escorsim Machado^b ; Jamila Alessandra Perini^a ; ^b ; ^{jamilaperini@yahoo.com.br}
• 关键词：Angiogenesis ; Endometriosis ; VEGFR2 ; VEGF ; Polymorphisms
• 刊名：European Journal of Obstetrics & Gynecology and Reproductive Biology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：209
• 期：Complete
• 页码：25-33
• 全文大小：667 K
• 卷排序：209

文摘

Endometriosis is a multifactorial gynecological disease, whose pathogenesis is crucially dependent on angiogenesis, which is signaled via vascular endothelial growth factor (VEGF) and its receptor (VEGFR2). We hypothesize that single nucleotide polymorphisms (SNPs) in VEGF and VEGFR2 genes may influence the onset and/or the progression of endometriosis. The main aim of this study was to investigate the contribution of VEGF and VEGFR2 SNPs as risk factors for endometriosis, as well as their association with endometriosis symptoms.Study designA case-control study was conducted, involving 293 endometriosis patients and 223 controls, who were submitted to laparoscopic or laparotomy surgery at hospitals from the Brazilian public health system. Genotyping of VEGF (−2578C > A, −460T > C, −1154G > A, +405G > C and +936C > T) and VEGFR2 (−604T > C, 1192C > T) SNPs was performed by TaqMan real-time polymerase chain reaction. The association between SNPs and endometriosis, deep infiltrating endometriosis (DIE) or endometriosis symptoms was estimated by odds ratios (OR) with their 95% confidence intervals (CI), which were calculated using multivariate logistic regression models.ResultsVEGF variant alleles −2578A and −1154A were associated with increased endometriosis risk (OR: 1.39, 95% CI: 1.04–1.87 and OR: 1.63, 95% CI: 1.12–2.37, respectively), whereas VEGF 405C and VEGFR2 1192T were associated with lower risk of endometriosis (OR: 0.66, 95% CI: 0.43–1.00 and OR: 0.58, 95% CI: 0.40–0.84, respectively). The combination of wild-type genotypes of both VEGF −2578C > A and −1154G > A with variant genotypes of both VEGF +405G > C and VEGFR2 1192C > T showed the best protective effect against the development of endometriosis, either considering all cases (OR: 0.33, 95% CI: 0.12–0.89) or only DIE (OR: 0.30, 95% CI: 0.10–0.87). The combination of variant genotypes of VEGF −2578C > A, −1154G > A, +405G > C and VEGFR2 1192C > T was also protective against DIE (OR: 0.67, 95% CI: 0.46–0.96). VEGFR2 1192C > T were associated with reduced cyclical urinary complaints (OR: 0.40, 95% CI: 0.18–0.88).ConclusionsOur results indicate that VEGF SNPs −2578C > A and −1154G > A increase endometriosis risk, whereas VEGF +405G > C and VEGFR2 1192C > T are protective against disease development, with VEGFR2 1192C > T also reducing cyclical urinary symptoms. The combined analysis of VEGF–VEGFR2 genotypes suggests a gene–gene interaction in endometriosis susceptibility.