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

Background: Endometriosis is regarded as a complex and heterogeneous disease in which genetic and eri'jironr>ental 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 roost common VEGF polyroorphisms. Methods: This study was conducted at two hospitals from the Brazilian public health system, and comprised 294 vvomen 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 TagMan cal time polymerase chain reaction. The odds ratio (OR) with their 957o confidence intervals (Cl) were calculated using an unconditional logistic regression model. Results: Endometriosis patients and controls did not differ regarding age distribution, whereas the body mass index was significantly lower in enciometriosis patients, when compared with controls (23.1 3.9 versus 27.3 5.9, P <0001). 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% Cl: 1.23 2.97), deep infiltrating endometriosis (DIE) (OR: 1.83, 95% Cl: 1.16-2.90) or moderate and severe endometriosis (stages Ill l5 (OR: 1.97, 95% Cl: 1.21-3.19). No significant differences were found in allele or genotype distributions of the 2578C > A, 460 T> C, +4070> C and +9,36C > T polymorphisms between endometriosis cases and controls. A total of six haplotypes were inferred derived from four polymorphisms (-2578C > A, 460 T> C, 1 1540 > A and +4050> C). There was a protective association between CCGG haplotype and endometriosis, either considering all cases (OR: 0.36, 95% Cl: 0.15-0.86), DIE (OR: 0.37 95% Cl: 0.15 0.90) or stages Ill IV (OR: 0.35 953 Cl: 0.13 ---- 0.95). Conclusions: The present results indicate a positive association between VEGF '11540 > A and the risk of developing endometriosis, whereas the CCGG haplotype may be protective against the development of disease.