Association of vascular endothelial growth factor (VEGF) Gene polymorphisms and expression with the risk of endometriosis: a case-control study

Endometriosis is a polygenic and multifactorial gynecology situation which might be associated with angiogenesis. In the current study we assess the role of vascular endothelial growth factor (VEGF) − 2578 A/C, and + 936 C/T polymorphisms in susceptibility to endometriosis and checking the expression of VEGF mRNA in eutopic tissue of endometrium with and without endometriosis. The study was comprised of 300 patients who underwent laparascopic or laparotomy surgery with 100 cases who had confirmed histological diagnosis of endometriosis, and 200 controls with no histological diagnosis of disease. The genotyping of VEGF polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) technique and the gene expression in tissue was determined using Real-Time PCR assay. There was no important difference of allele distribution of the − 2578 A/C (P = 0.7) and + 936 C/T (P = 0.5) polymorphisms among endometriosis cases and controls. Study of VEGF expression during the menstrual cycle, showed that endometrial tissue in cases group expressed more VEGF mRNA at the secretory phase compared to the proliferative phase (P = 0.03). Our results suggest that − 2578 A/C and + 936 C/T polymorphisms of VEGF did not seem to have impact on endometriosis predisposition in our study population. Also we did not find any link between VEGF mRNA expression and risk of endometriosis. Similar content being viewed by others

Hsieh Y-Y, Chang C-C, Tsai F-J, Yeh L-S, Lin C-C, Peng C-T (2004) T allele for VEGF gene-460 polymorphism at the 5′-untranslated region: association with a higher susceptibility to endometriosis. J Reprod Med 49(6):468–472 Bhanoori M, Babu KA, Reddy NP, Rao KL, Zondervan K, Deenadayal M, Kennedy S, Shivaji S (2005) The vascular endothelial growth factor (VEGF) + 405G > C 5′-untranslated region polymorphism and increased risk of endometriosis in South Indian women: a case control study. Hum Reprod 20(7):1844–1849 Fritz MA, Speroff L (2011) Clinical gynecologic endocrinology and infertility. Lippincott Williams & wilkins, Philadelphia Zhang F, Yang Y, Wang Y (2012) Association between TGF-β1-509C/T polymorphism and endometriosis: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 164(2):121–126 Donnez J, Smoes P, Gillerot S, Casanas-Roux F, Nisolle M (1998) Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod 13(6):1686–1690 Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25(4):581–611 Di Carlo C, Bonifacio M, Tommaselli GA, Bifulco G, Guerra G, Nappi C (2009) Metalloproteinases, vascular endothelial growth factor, and angiopoietin 1 and 2 in eutopic and ectopic endometrium. Fertil Steril 91(6):2315–2323 Tan X-J, Lang J-H, Liu D-Y, Shen K, Leng J-H, Zhu L (2002) Expression of vascular endothelial growth factor and thrombospondin-1 mRNA in patients with endometriosis. Fertil Steril 78(1):148–153 Gilabert-Estellés J, Ramón L, Espana F, Gilabert J, Vila V, Réganon E, Castelló R, Chirivella M, Estellés A (2007) Expression of angiogenic factors in endometriosis: relationship to fibrinolytic and metalloproteinase systems. Hum Reprod 22(8):2120–2127 Vigano P (2003) Perspectives on endometriosis: new physiopathologic approaches and treatments. J Gynecol Obstet Biol Reprod 32(8 Pt 2):S28–S31 Zhao ZZ, Nyholt DR, Thomas S, Treloar SA, Montgomery GW (2008) Polymorphisms in the vascular endothelial growth factor gene and the risk of familial endometriosis. Mol Hum Reprod 14(9):531–538 Li Y, Wang L, Li X, Li S, Wang J, Wu Z, Gong L, Zhang X (2013) Vascular endothelial growth factor gene polymorphisms contribute to the risk of endometriosis: an updated systematic review and meta-analysis of 14 case–control studies. Genet Mol Res 12(2):1035–1044 Xu S, Wu W, Sun H, Lu J, Yuan B, Xia Y, De Moor B, Marchal K, Wang X, Xu P (2012) Association of the vascular endothelial growth factor gene polymorphisms (– 460C/T, + 405G/C and + 936T/C) with endometriosis: a meta-analysis. Ann Hum Genet 76(6):464–471 Liang S, Huang Y, Fan Y (2012) Vascular endothelial growth factor gene polymorphisms and endometriosis risk: a meta-analysis. Arch Gynecol Obstet 286(1):139–146 Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE (2000) Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 12(8):1232–1235 Krippl P, Langsenlehner U, Renner W, Yazdani-Biuki B, Wolf G, Wascher TC, Paulweber B, Haas J, Samonigg H (2003) A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk. Int J Cancer 106(4):468–471 Jin Q, Hemminki K, Enquist K, Lenner P, Grzybowska E, Klaes R, Henriksson R, Chen B, Pamula J, Pekala W (2005) Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis. Clin Cancer Res 11(10):3647–3653 Yang B, Cross DF, Ollerenshaw M, Millward BA, Demaine AG (2003) Polymorphisms of the vascular endothelial growth factor and susceptibility to diabetic microvascular complications in patients with type 1 diabetes mellitus. J Diabetes Complicat 17(1):1–6 Shahbazi M, Fryer A, Pravica V, Brogan I, Ramsay H, Hutchinson I, Harden P (2002) Polymorphisms in vascular endothelial growth factor gene are associated with increased risk of acute rejection in renal transplant recipients. J Am Soc Nephrol 1:260–264 Mohammadi M, Ollier WE, Hutchinson IV (2003) A functional association study of VEGF gene promoter polymorphisms with VEGF expression by stimulated pbm cells. Hum Immunol 64(10):S125 Qing L, Yan L, Jian Z, DongLan S, YaNan D, Na W, RongMiao Z, Shan K (2009) Association of polymorphisms − 1154 G/A and − 2578 C/A in the vascular endothelial growth factor gene with decreased risk of endometriosis in Chinese women. Hum Reprod 24(10):2660–2666 Cosín R, Gilabert-Estellés J, Ramón LA, España F, Gilabert J, Romeu A, Estellés A (2009) Vascular endothelial growth factor polymorphisms (− 460C/T, + 405G/C, and 936C/T) and endometriosis: their influence on vascular endothelial growth factor expression. Fertil Steril 92(4):1214–1220 Kim JG, Kim JY, Jee BC, Suh CS, Kim SH, Choi YM (2008) Association between endometriosis and polymorphisms in endostatin and vascular endothelial growth factor and their serum levels in Korean women. Fertil Steril 89(1):243–245 Kim SH, Choi YM, Choung SH, Jun JK, Kim JG, Moon SY (2005) Vascular endothelial growth factor gene + 405 C/G polymorphism is associated with susceptibility to advanced stage endometriosis. Hum Reprod 20(10):2904–2908 Bourlev V, Volkov N, Pavlovitch S, Lets N, Larsson A, Olovsson M (2006) The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions. Reproduction 132(3):501–509

The authors thank the collaboration of the patients in this study. In addition, laboratory work was done in Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences (TUMS) at Shariati Hospital. This work was supported by Vali-e-Asr Reproductive Health Research Centre, Tehran University of Medical Sciences. Author information Authors and Affiliations Corresponding authors Ethics declarations Conflict of interest All authors of original research article declare that they have no conflict of interest. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article Rashidi, B.H., Sarhangi, N., Aminimoghaddam, S. et al. Association of vascular endothelial growth factor (VEGF) Gene polymorphisms and expression with the risk of endometriosis: a case–control study. Mol Biol Rep 46, 3445–3450 (2019). https://doi.org/10.1007/s11033-019-04807-6 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11033-019-04807-6