Avaliação da influência dos polimorfismos no gene do fator decrescimento endotelial vascular e seu receptor na etiologia da endometriose

Endometriosis is considered a complex diseases influenced by both genetic and environmental factors. The angiogenesis via signaling vascular endothelial growth factor (VEGF) and its kinase insert domain receptor (KDR), is a crucial process in the establishment and progression of endometriosis. Single nucleotide polymorphisms (SNPs) in VEGF and KDR genes can influence the development of the disease. This study aimed to evaluate the role of VEGF (- 2578C>A, -460T>C, -1154G>A +405G>C and +936C>T) and KDR (-604T>C, 1192C>T and 1719T>A) SNPs in the etiology of endometriosis. The study population consisted of 293 women with histopathological diagnosis of endometriosis (cases) and 223 women without laparoscopic evidence of disease (controls). Genotyping of the studied SNPs was performed by polymerase chain reaction (PCR) in real time using the TaqMan system. Logistic regression was used, being obtained odds ratios (OR) and confidence intervals (95% CI) to evaluate the associations of the studied SNPs and the development of endometriosis, and the presence of symptoms. Positive association of VEGF -2578C>A and -1154G>A SNPs with the development of endometriosis was observed (OR: 1,88; 95% CI: 1,06 - 3,36; OR: 1,59; 95% CI: 1,03 - 2,45, respectively), whereas VEGF+405G>C and KDR1192C>T SNPs were negatively associated with the disease (OR: 0,66; 95% CI: 0,43 - 1.00; OR: 0,56; 95% CI: 0,39 - 0,81, respectively). It was found a protective effect of VEGF (CTGC, ATGG and GGCC) and KDR (TTT and CTA) haplotypes susceptibility to endometriosis; and an increased risk of VEGF (ACAG) and KDR (CCA and TCA) haplotypes with the development of the disease. Negative association was found in the combined genotypes of VEGF and KDR with the development of endometriosis and the presence of symptoms (dysmenorrhea, pelvic pain, dyspareunia and urinary symptoms). It was also carried out a systematic review using the STROBE system on the association of VEGF and KDR SNPs in the development of endometriosis, and describes the methodological differences of case-control studies. In conclusion VEGF and KDR SNPs are associated with the development of endometriosis and its symptoms, suggesting that signaling pathway, VEGF-KDR, is an important factor in the etiology of the disease. This study serves as a database for future applications for the development of biomarkers for the diagnosis and / or prognosis of endometriosis.