title: 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 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  Endometriosis 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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Laboratório de Pesquisa de Ciências Farmacêuticas, Unidade de Farmácia, Centro Universitário Estadual da Zona Oeste, Av, Manoel Caldeira de Alvarenga, 1203, Campo Grande, Rio de Janeiro, RJ 23070-200, Brasil. jamilaperini@yahoo.com.br.
authors.forename: Jamila Alessandra
authors.initials: JA
authors.lastname: Perini
authors.forename: Jessica Vilarinho
authors.initials: JV
authors.lastname: Cardoso
authors.forename: Plínio Tostes
authors.initials: PT
authors.lastname: Berardo
authors.forename: Rosane
authors.initials: R
authors.lastname: Vianna-Jorge
authors.forename: Luiz Eurico
authors.initials: LE
authors.lastname: Nasciutti
authors.forename: Marta
authors.initials: M
authors.lastname: Bellodi-Privato
authors.forename: Daniel Escorsim
authors.initials: DE
authors.lastname: Machado
authors.forename: Mauricio Simões
authors.initials: MS
authors.lastname: Abrão
mesh_terms: D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D004715:Endometriosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A