Genetic Polymorphism in the Fibrinolytic System and Endometriosis

Mohamed A Bedaiwy, Tommaso Falcone, Edward J Mascha, Robert F Casper
Obstetrics and gynecology · 2006 · vol. 108(1) , pp. 162–168 · doi:10.1097/01.aog.0000220517.53892.0a · PMID:16816071 · W2075432395
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The 4G allele of the PAI-1 gene, associated with hypofibrinolysis, was significantly more prevalent in women with endometriosis, suggesting a role in lesion initiation.

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Abstract

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%; 95% 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. LEVEL OF EVIDENCE: II-2.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Fibrin Fibrinolysis Plasminogen Activator Inhibitor 1 Polymorphism, Genetic Adult Alleles Endometriosis Endometriosis Female Fibrin Fibrinolysis Genetic Variation Genotype Humans Infertility Infertility Multivariate Analysis Pain Pain

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