The Single Nucleotide Polymorphisms (SNPS) of Vascular Endothelial Growth Factor (VEGF) Gene and Endometriosis
Abstract
Aim: The aim of the present work was to evaluate associations between the risk of endometriosis and -460C/T (rs833061) and +405G/C (rs2010963) polymorphisms in the VEGF gene.
Methodology : In the present study, we examined group of 100 patients with endometriosis and 100 controls. Genomic DNA was extracted from peripheral blood. Determination of genes polymorphic variants was made using polymerase chain reaction -restriction fragment length polymorphism technique (PCR -RFLP).
Results: Presented study showed statistically significant increase in the endometriosis development risk for the -460T/T genotype (OR 3.39; 95% CI, 1.60 -7.13; p = 0.002) and for the -460T allele (OR 2.49; 95% CI , 1.64 -3.78; p <.0001), as well as for the +405C/C genotype (OR 2.16; 95% CI, 1.047 -4.48; p = 0.035) in patients with endometriosis in comparison with healthy control group. We also observed positive association of the +405C/C genotype (OR 0.26; 95% CI, 0. 08-0.79; p = 0.019) as well as the +405C allele occurrence with an increased endometriosis development risk (OR 0.31; 95% CI, 0.19 - 0.71; p = 0.005), assessed by the degree of rASRM classification stages.
Conclusion : The results support the hypothesis that the -460C/T and +405G/C polymorphisms of the VEGF gene may be associated with endometriosis occurrence in Poland.
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Introduction
Endometriosis is a common gynaecological disease of unknown aetiology. Endometriosis is a multifactorial and polygenic disease. Angiogenesis (the growth of blood vessels from pre-existing vasculature) is considered as a major process in the pathogenesis of endometriosis. Many factors are involved in this complex mechanism such as cytokines (interleukins IL-1, IL-6, IL-8, Tumor Necrosis Factor α (TNFα)), metalloproteinases (MMP1, MMP-3, MMP-9) and vascular endothelial growth factors family (VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F) [1, 2].
VEGF is one of the most potent and specific angiogenic factors. VEGF is responsible for increased vascular permeability and the proliferation of endothelial cells [3]. There are many causes indicating the role of vascular endothelial growth factor in the development of endometriosis, such as expression of VEGF in stromal and epithelial cells and its regulation by estrogen receptors α and β [4, 5].
Elevated concentrations of VEGF have been detected in the peritoneal fluid of patients with endometriosis [6-9].
VEGF gene has been mapped to chromosome 6p21.3 and is polymorphic in nature [10-12]. Polymorphisms within the 5′untranslated region (5-’UTR) lead to differences in VEGF expression level between individuals and could influence the aetiology of a variety of pathological conditions with which VEGF has been associated. Several transcription factor-binding sites are found in the VEGF 5′-UTR and variation within the region increases the transcriptional activity [13].
Single nucleotide polymorphisms (SNPs) within the VEGF gene have been identified, some of which have functional significance [14, 15]. Two common VEGF single nucleotide polymorphisms, +405G/C (rs2010963) and -460C/T (rs833061) in the 5-′UTR have been reported to be associated with altered gene transcription [16, 17].
In the literature, many reports confirm the significance VEGF gene -460C/T and +405G/C polymorphism, regarding the risk of endometriosis [18-29]. However, the reported results have rather been inconsistent [30, 31].
Little is known on the association between VEGF polymorphisms and endometriosis in Polish women. In the present work we analysed an association between endometriosis and two single nucleotide polymorphisms occurring in VEGF gene: 460C/T and +405G/C, respectively.
Conclusion
In conclusion, the presented study implies that -460C/T and +405G/C polymorphisms of the VEGF gene may be associated with endometriosis in Polish women. The study was carried out on a relatively small patient population, thus the obtained results cannot be considered as definitive and require further, more extensive evaluations, performed on bigger groups of patients. However, our preliminary results are fairly promising, indicating a significant role of the polymorphisms of VEGF genes for endometriosis development. It also appears from a thorough review of the medical literature that the polymorphisms in VEGF gene , involved in the angiogenesis pathway, have for the first time been analyzed in endometriosis patients in Poland. Thus we feel that our observations may be an important signal, prompting to appreciate the role of VEGF in endometriosis occurrence and likely triggering further studies on this interesting subject.
