Role of vascular endothelial growth factor polymorphisms (-2578C > A, -460 T > C, -1154G > A, +405G > C and +936C > T) in endometriosis: a case–control study with Brazilians

Abstract

BackgroundEndometriosis is regarded as a complex and heterogeneous disease in which genetic and environmental factors contribute to the phenotype. The Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of endometriosis. The present study was aimed at investigating the contribution of VEGF polymorphisms as risk factors for the development of endometriosis. This is the first study to evaluate the combined influence of the five most common VEGF polymorphisms.MethodsThis study was conducted at two hospitals from the Brazilian public health system, and comprised 294 women submitted to laparoscopic or laparotomy surgery: 182 patients had a histologically confirmed diagnosis of endometriosis (cases), whereas 112 had no evidence of the disease (controls). The VEGF polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model.ResultsEndometriosis patients and controls did not differ regarding age distribution, whereas the body mass index was significantly lower in endometriosis patients, when compared with controls (23.1 ± 3.9 versus 27.3 ± 5.9, P < 0.001). The evaluation of gynecological symptoms, including dysmenorrhea, non-cyclic chronic pelvic pain, dyspareunia and infertility, indicates significantly higher prevalences among endometriosis cases. The variant allele -1154A was significantly associated with endometriosis, either considering all cases (OR: 1.90, 95% CI: 1.23–2.97), deep infiltrating endometriosis (DIE) (OR: 1.83, 95% CI: 1.16-2.90) or moderate and severe endometriosis (stages III-IV) (OR: 1.97, 95% CI: 1.21-3.19). No significant differences were found in allele or genotype distributions of the –2578C > A, -460 T > C, +405G > C and +936C > T polymorphisms between endometriosis cases and controls. A total of six haplotypes were inferred derived from four polymorphisms (-2578C > A, -460 T > C, -1154G > A and +405G > C). There was a protective association between CCGG haplotype and endometriosis, either considering all cases (OR: 0.36, 95% CI: 0.15–0.86), DIE (OR: 0.37 95% CI: 0.15 – 0.90) or stages III-IV (OR: 0.35 95% CI: 0.13 – 0.95).ConclusionsThe present results indicate a positive association between VEGF -1154G > A and the risk of developing endometriosis, whereas the CCGG haplotype may be protective against the development of disease.

The −2549 insertion/deletion polymorphism of VEGF gene associated with uterine leiomyoma susceptibility in women from Southeastern Iran

“…There was an association between VEGF +936 C/T polymorphism, but not VEGF -460 C/T, +405 G/C polymorphisms and endometriosis in Tunisian population in the study of Henidi et al [27]. Perini et al showed an association between VEGF -1154G > A polymorphism and the risk of developing endometriosis in Brazil [28].…”

Polymorphisms in VEGF and KDR genes in the development of endometriosis: a systematic review

“…17 Thus, 11 case-control studies were included in this review that evaluated SNPs only in VEGF gene susceptibility to develop endometriosis from 2005 to 2015. 8,21,23,24,26,27,[31][32][33]36,37 In relation to evaluate the quality of 11 studies selected for this review, all the articles reached a percentage greater than 50% 38 and the average score ranged between 12 to 21 points (55-96%). The studies that had the lowest and the highest score, according to the STROBE criteria were Kim et al 24 and Perini et al, 8 respectively (Table 1).…”

“…5 Women with endometriosis may be asymptomatic (10.7%), however, most of them present symptoms in different intensities, the main ones are: dysmenorrhoea (52-97%), chronic pelvic pain (22-69%), infertility (25-59%), dyspareunia (44-71%) and intestinal symptoms (71%) and cyclic urinary (60%). [6][7][8] Endometriosis causes physical, mental and social consequences to women, bearing in mind that their psyche, interpersonal and martial relationships are affected by the problems of the symptoms, in particularly, by the difficulty of bearing children. 9 There are several theories explaining about the appearance of endometriosis; however its etiology is still not clear.…”

“…[15][16][17][18] Recently, our group observed a positive association for VEGF rs1570360 SNP in the development of endometriosis (OR: 1.90; CI95%: 1.23-2.97) in Brazilian women. 8 Several case-control studies also investigated the influence of SNPs in VEGF or KDR genes in the development of endometriosis. 8,17,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] However, the results of the analysis are still controversial.…”

“…8 Several case-control studies also investigated the influence of SNPs in VEGF or KDR genes in the development of endometriosis. 8,17,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] However, the results of the analysis are still controversial. In this context, the aim of this study was to review all the studies that used case-control design to investigate the magnitude of SNPs association of VEGF and/or KDR genes susceptibility to develop endometriosis, in order to discuss the possible causes of the conflicting results already described.…”