MAIN RESEARCH ARTICLE Plasminogen activator inhibitor-1 4G/5G polymorphism in infertile women with and without endometriosis RUBENS P. GONC ¸ALVES-FILHO, ARIEL BRANDES, DENISE M. CHRISTOFOLINI, TATIANA G. LERNER, BIANCA BIANCO & CAIO P. BARBOSA Division of Gynecological Pathology and Human Reproduction, Department of Gynecology and Obstetrics, Faculty of Medicine of ABC (Santo Andr ´ e, S ˜ ao Bernardo do Campo and S ˜ ao Caetano do Sul County), Santo Andr ´ e, Sao Paulo, Brazil Key words Endometriosis, fibrinolytic system, infertility, plasminogen activator inhibitor-1, polymorphism Correspondence Caio Parente Barbosa, Avenida Principe de Gales, 821 – Santo Andr ´ e/SP, Brazil – CEP: 09060-650. E-mail: caiopb@uol.com.br Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article. Received: 27 August 2010 Accepted: 23 January 2011 DOI: 10.1111/j.1600-0412.2011.01086.x Abstract Objective. To evaluate PAI-1 genotypes in a group of infertile women with or with- out endometriosis and control subjects. Design. Case–control study. Setting . Human Reproduction Center of Medicina do ABC Faculty. Population. One hundred and forty infertile women with endometriosis, 64 women with idiopathic infertility and 148 fertile women as control subjects. Methods. The PAI-1 4G/5G polymor- phism was identified by restriction fragment length polymorphism–polymerase chain reaction. Main outcome measures. Genotype distribution and allele frequency of the 4G/5G polymorphism of the PAI-1 gene. Results. The frequencies of geno- types 4G/4G, 4G/5G and 5G/5G of the PAI-1 gene in the infertile women with endometriosis were 38.6, 37.1 and 24.3%, respectively, and in the control group 24.3, 33.8 and 41.9%, respectively (p=0.003). When the infertile women with en- dometriosis were divided according to their endometriosis stage, genotypes 4G/4G, 4G/5G and 5G/5G were identified, respectively, in 36.7, 32.9 and 30.4% of the patients with minimal/mild endometriosis (p=0.102) and in 41.0, 42.6 and 16.4% of the patients with moderate/severe endometriosis (p=0.001); in the women with idiopathic infertility, these genotypes were found at a frequency of 29.7, 34.3 and 36%, respectively (p=0.637). Conclusion. The data suggest that, in Brazilian women, the PAI-1 4G/5G polymorphism may be associated with a risk of endometriosis- associated infertility. Abbreviations: CI, confidence interval; EDTA, ethylenediamine tetraacetic acid; G, guanine; MgCl 2 , magnesium chloride; OR, odds ratio; PA, plasminogen activator; PAI-1ag, plasminogen activator inhibitor-1 antigen; PAI-1 gene, plasminogen activator inhibitor-1 gene; RFLP–PCR, restriction fragment length polymorphism–polymerase chain reaction; SERPIN, serine protease inhibitor; tPA, tissue-type plasminogen activator. Introduction Endometriosis is a common gynecological disease, defined as the growth of endometrial tissue outside the uterine cavity, that often results in a vast array of gynecological problems, including dyspareunia, dysmenorrhea, pelvic pain and infer- tility (1,2). Previous studies have revealed a great number of genetic markers related to the immune, neuroendocrine and reproductive function and of gene interactions, indicating an association between the development of endometriosis and genetic polymorphisms (3–5). The fibrinolytic system includes a broad spectrum of pro- teolytic enzymes with physiological and pathophysiological functions such as fibrinolysis, tissue remodeling, tumor in- vasion, and also participation in the reproductive process (6,7). The plasminogen activator inhibitor-1 (PAI-1) gene, a member of the serine protease inhibitor family, is a main reg- ulator of the endogenous fibrinolytic system. It inhibits the c  2011 The Authors Acta Obstetricia et Gynecologica Scandinavica c  2011 Nordic Federation of Societies of Obstetrics and Gynecology 1 A C TA Obstetricia et Gynecologica