Genetic polymorphism in the fibrinolytic system and endometriosis
Genetic polymorphism in the fibrinolytic system and endometriosis
复制标题
DOI：
10.1097/01.aog.0000220517.53892.0a
复制
发表时间：
2006-07-01
影响因子：
7.2
通讯作者：
Casper, Robert F.
中科院分区：
文献类型：
--
作者：
Bedaiwy, Mohamed A.;Falcone, Tommaso;Casper, Robert F.
目的：尽管大多数女性在生育期间都会经历月经逆行，但只有一小部分女性会出现子宫内膜异位症。我们假设，由于纤维蛋白溶解不足，纤维蛋白基质在腹膜袋中持续存在，可能会使月经沉积的子宫内膜碎片引发子宫内膜异位症。纤维蛋白溶解受到多种因素的调节，纤溶酶原激活物抑制剂-1 (PAI-1) 基因的多态性被认为是重要的决定因素之一。本研究的目的是评估一组患有或不患有子宫内膜异位症的女性的 PAI-1 基因型。 方法：从 118 名女性（75 名腹腔镜确诊的子宫内膜异位症女性和 43 名对照女性）中，从血液中提取基因组 DNA，并使用 4G 或 5G 等位基因的特异性引物通过聚合酶链反应扩增 DNA，然后进行凝胶电泳来确定 PAI-1 启动子基因型。对部分聚合酶链式反应产物进行纯化和测序，以确认凝胶电泳结果。 结果：与 5G/5G PAI-1 基因型相比，4G/5G（比值比 38；95% 置信区间 [CI] 6-229）或 4G/4G（比值比 441；95% CI 53-3,694）患者更容易发生子宫内膜异位症。 75 名患有子宫内膜异位症的女性中有 52 名（69%，95% CI 58-79%）具有 4G/4G 基因型，而 43 名对照女性中只有 5 名（12%；95% CI 4-25%）具有 4G/4G 基因型。相比之下，75 名患有子宫内膜异位症的女性中，有 2 名（3%；950% CI 0-9%）发现了与正常纤溶相关的 5G/5G 基因型，而 43 名对照女性中，有 24 名（56%；95% CI 40-71%）发现了与正常纤溶相关的 5G/5G 基因型。与对照组相比，子宫内膜异位症。纤维蛋白基质的持续存在可能支持腹腔内子宫内膜异位病变的发生，这解释了为什么一些月经逆行的女性会患上子宫内膜异位症，而另一些女性则不会。
OBJECTIVE: Although most women experience retrograde menses during their reproductive life, endometriosis develops only in a small percentage. We hypothesized that persistence of a fibrin matrix in peritoneal pockets, as a result of hypofibrinolysis, could allow menstrually deposited endometrial fragments to initiate endometriosis. Fibrinolysis is modulated by several factors, and polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) gene are considered to be one of the important determinants. The objective of this study was to evaluate PAI-1 genotypes in a group of women with or without endometriosis.METHODS: In 118 women (75 with laparoscopically confirmed endometriosis and 43 controls), genomic DNA was extracted from blood and the PAI-1 promoter genotype was determined by polymerase chain reaction amplification of DNA using specific primers for the 4G or 5G allele followed by gel electrophoresis. A portion of the polymerase chain reaction product was purified and sequenced to confirm the gel electrophoresis results.RESULTS: Endometriosis was more likely in patients with 4G/5G (odds ratio 38; 95% confidence interval [CI] 6-229) or 4G/4G (odds ratio 441; 95% CI 53-3,694) compared with 5G/5G PAI-1 genotype. Fifty-two of 75 women with endometriosis (69 %, 95% CI 58-79%) had the 4G/4G genotype compared with only 5 of 43 (12%; 95% CI 4-25%) controls. In contrast, the 5G/5G genotype associated with normal fibrinolysis was found in 2 of 75 (3%; 950% CI 0-9%) women with endometriosis compared with 24 of 43 (56%; 95% CI 40-71%) controls.CONCLUSION: Hypofibrinolysis, associated with the 4G allele of the PAI-1 gene, was found significantly more often in women with endometriosis compared with controls. Persistence of fibrin matrix could support the initiation of endometriotic lesions in the peritoneal cavity, explaining why some women with retrograde menstruation develop endometriosis while others do not.