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.
BMC Womens Health. 2014 Sep 26;14:117. doi: 10.1186/1472-6874-14-117.
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.
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.
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).
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.
子宫内膜异位症被认为是一种复杂且异质的疾病，其中遗传和环境因素促成了表型。血管内皮生长因子（VEGF）在子宫内膜异位症的发病机制中起着重要作用。本研究旨在探讨 VEGF 多态性作为子宫内膜异位症发病风险因素的作用。这是第一项评估五个最常见 VEGF 多态性联合影响的研究。
本研究在巴西公共卫生系统的两家医院进行，共纳入 294 名接受腹腔镜或剖腹手术的女性：182 名患者组织学确诊为子宫内膜异位症（病例），112 名患者无疾病证据（对照）。采用 TaqMan 实时聚合酶链反应检测 VEGF 多态性。使用无条件逻辑回归模型计算比值比（OR）及其 95%置信区间（CI）。
子宫内膜异位症患者和对照组在年龄分布上无差异，而子宫内膜异位症患者的体重指数明显低于对照组（23.1±3.9 与 27.3±5.9，P<0.001）。妇科症状（痛经、非周期性慢性盆腔痛、性交困难和不孕）的评估表明，子宫内膜异位症病例的患病率明显更高。变体等位基因-1154A 与子宫内膜异位症显著相关，无论是考虑所有病例（OR：1.90，95%CI：1.23-2.97）、深部浸润性子宫内膜异位症（DIE）（OR：1.83，95%CI：1.16-2.90）还是中重度子宫内膜异位症（III-IV 期）（OR：1.97，95%CI：1.21-3.19）。病例和对照组之间 VEGF-2578C> A、-460T> C、+405G> C 和+936C> T 多态性的等位基因或基因型分布无显著差异。从四个多态性（-2578C> A、-460T> C、-1154G> A 和+405G> C）推断出六个单倍型。CCGG 单倍型与子宫内膜异位症呈保护相关，无论是考虑所有病例（OR：0.36，95%CI：0.15-0.86）、DIE（OR：0.37，95%CI：0.15-0.90）还是 III-IV 期（OR：0.35，95%CI：0.13-0.95）。
本研究结果表明 VEGF-1154G> A 与子宫内膜异位症的发病风险呈正相关，而 CCGG 单倍型可能对疾病的发生具有保护作用。
