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PubMed2004

Association rate between deep peritoneal endometriosis and other forms of the disease: pathogenetic implications.

BACKGROUND: It has been suggested recently that deep endometriosis and the other forms of the disease do not share a common pathogenetic mechanism. In this study, we hypothesize that, if this is true, deep peritoneal endometriosis and the other forms should not be significantly associated. METHODS: Clinical and surgical records of all women who were referred to the Department of Obstetrics and Gynecology, Clinica 'L.Mangiagalli' between January 1995 and June 2002 and who were diagnosed with deep peritoneal pelvic endometriosis at the time of surgery were retrieved. The concomitant presence of superficial endometriotic implants, endometriomas and pelvic adhesions was evaluated. A binomial probability distribution model was used to calculate the 95% confidence interval (95% CI) of the association rates. RESULTS: Ninety-three women with deep peritoneal endometriosis were identified. The presence of superficial endometriotic implants, endometriomas and pelvic adhesions was documented in 61.3% (95% CI 51.4-71.2%), 50.5% (95% CI 40.3-60.7%) and 74.2% (95% CI 65.3-83.1%) of patients with deep endometriotic nodules, respectively. Overall, deep peritoneal endometriosis was the only form of the disease in only 6.5% (95% CI 2.8-12.3%) of cases. No relevant differences regarding these associations were observed according to the location and the size of the deep endometriotic nodules. CONCLUSIONS: Results from this study do not support the hypothesis that deep endometriosis should be considered as a distinct entity of the disease.

Adnexal Diseases↗

PubMed2005

Possible implication of midkine in the development of endometriosis.

BACKGROUND: The present study was conducted to assess whether midkine (MK), a multifunctional molecule known to stimulate tumor growth, may be involved in the development of endometriosis. METHODS: The mitogenic activity of MK on cultured endometriotic stromal cells was examined by measuring 5-bromo-2'-deoxyuridine (BrdU) incorporation. Concentrations of MK in the peritoneal fluid (PF) of women without or with endometriosis and those under GnRH agonist treatment were measured using a specific enzyme immunoassay. The expression of MK mRNA in peritoneal bone marrow-derived cells, peritoneum and endometriotic tissues was evaluated by RT-PCR. RESULTS: MK significantly increased BrdU incorporation into the DNA of cultured endometriotic stromal cells. The MK concentrations in the PF of the women with advanced endometriosis (stages II, III and IV) Median: 1.21 ng/ml; interquartile range 0.80-2.27 were significantly higher than those of the women without endometriosis and with stage I endometriosis (0.06 ng/ml, 0.67-1.26, P < 0.05). As for the menstrual phase, the MK concentration in PF in the inteal phase (1.32 ng/ml. 0.72-2.21) were significantly higher than those in the follicular phase (0.95 ng/ml, 0.68-1.24, P < 0.05). In addition, women with adnexal adhesions had higher concentrations of MK in PF than those without adhesions (P < 0.05). The MK concentrations of the women under GnRH agonist treatment were significantly lower than those of the other groups (P < 0.001). The expression of MK mRNA was detected in peritoneal bone marrow-derived cells, peritoneum and endometriotic tissues. CONCLUSIONS: The present findings suggest that MK may play roles, such as stimulation of endometriotic cell proliferation, in the development of endometriosis.

Adult↗

PubMed2005

Increased soluble interleukin-1 receptor type II proteolysis in the endometrium of women with endometriosis.

Numerous functional changes were observed in the intrauterine endometrial tissue of women with endometriosis. Our previous studies revealed a marked decrease in the expression of interleukin-1 receptor type 2 (IL-1RII), a decoy receptor known for its ability to buffer IL-1 effects. The aim of the present study was to assess whether post-translational mechanisms such as proteolysis may contribute to the down-regulation of IL-1RII levels. Our data showed that soluble IL-1RII (sIL-1RII) concentrations released by freshly cultured endometrial tissue were significantly lower in women with endometriosis than in normal women (P < 0.01) and further revealed a statistically significant correlation between increased proteolysis and decreased sIL-1RII levels (P < 0.05; r = -0.47). (125)I-labelled soluble recombinant human IL-1RII ([(125)I]srhIL-1RII) was significantly more degraded in culture supernatant of tissues from women with endometriosis compared to normal women (P < 0.05), and natural tissue inhibitor of matrix metalloproteinase (TIMP)-1 inhibited [(125)I]srhIL-1RII degradation. Incubation of srhIL-1RII with active rhMMP-9 resulted in a dose-dependent degradation of srhIL-1RII as analysed by western blotting. Dual immunofluorescence showed an increased immunostaining for matrix metalloproteinase-9 in situ in the endometrial tissue of women with endometriosis compared to normal women and a decreased immunostaining for IL-1RII. The present study showed a reduced release of sIL-1RII by the endometrial tissue of women with endometriosis and revealed a proteolytic post-translational mechanism which may be involved in the down-regulation of IL-1RII levels. This may enhance IL-1-mediated activation of endometrial cells and contribute to the local immuno-inflammatory process observed in endometriosis patients.

Adult↗

PubMed2005

Interleukin 1alpha and tissue-lytic matrix metalloproteinase-1 are elevated in ectopic endometrium of patients with endometriosis.

BACKGROUND: Matrix metalloproteinases (MMP) play an essential role in tissue remodelling and menstruation and appear to be regulated by cytokines such as interleukin-1alpha (IL-1alpha). In order to investigate their role in the pathogenesis of endometriosis, the aim of the present study was to compare the protein localization of matrix metalloproteinase-1 (MMP-1) and of its main stimulatory cytokine IL-1alpha in eutopic and dystopic endometrium of patients with endometriosis. METHODS: MMP-1 and IL-1alpha protein localization was analysed retrospectively in paired paraffin-embedded tissue biopsies obtained simultaneously from the endometrial cavity and from endometrial lesions of 37 patients with peritoneal or ovarian endometriosis and in cycling endometria from 37 women without endometriosis. Protein localization was demonstrated by immunohistochemistry; antibody specificity was confirmed by western blot analysis. RESULTS: MMP-1 and IL-1alpha protein staining in women suffering from endometriosis was significantly more pronounced in endometriotic lesions than in eutopic endometrium. This held true for both epithelial MMP-1 and IL-1alpha staining (P < 0.006 and P < 0.001), and for stromal MMP-1 and IL-1alpha staining (P < 0.001 and P < 0.001). Furthermore, stromal MMP-1 and IL-1alpha were significantly co-expressed in dystopic endometriotic tissue (P = 0.045). Endometrial MMP-1 and IL-1alpha protein expression pattern in eutopic endometrium from women suffering from endometriosis, however, did not differ significantly from the pattern seen in healthy women. CONCLUSIONS: The increased expression of both matrix-degrading MMP-1 and its major stimulatory cytokine IL-1alpha in endometriotic lesions and the selective co-expression in the stroma of endometriotic foci clearly suggests their involvement in the pathogenic mechanisms leading to local invasion and tissue destruction.

Adult↗

PubMed2005

Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis.

BACKGROUND: The objective of this multicentre randomized, controlled clinical trial was to compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a depot-GnRH-analogue in the control of endometriosis-related pain over a period of six months. METHODS: Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized using a computer-generated system of sealed envelopes into either LNG-IUS (n = 39) or GnRH analogue (n = 43) treatment groups at three university centres. Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale (VAS), daily bleeding score was calculated from bleeding calendars, and improvement in quality of life was evaluated using the Psychological General Well-Being Index Questionnaire (PGWBI). The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis. A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period. RESULTS: CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups (P > 0.999). In both treatment groups, women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease (P < 0.002). LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34% and 71% of patients in the LNG-IUS and GnRH-analogue groups, respectively, reporting no bleeding during the first treatment month, and 70% and 98% reporting no bleeding during the sixth month. No difference was observed between groups with reference to improvement in quality of life. CONCLUSIONS: Both, the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments. Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years. This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive.

Adolescent↗

PubMed2005

Interleukin-6- and tumour necrosis factor alpha-mediated expression of hepatocyte growth factor by stromal cells and its involvement in the growth of endometriosis.

BACKGROUND: We investigated the expression of the hepatocyte growth factor (HGF) gene and protein by the stromal cells derived from women with or without endometriosis and its regulation by interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFalpha). METHODS: Stromal cells immunoreactive to vimentin were isolated from the eutopic and ectopic endometrium of 18 infertile women with endometriosis and 12 women without endometriosis. The production of HGF in the culture media of basal and IL-6- or TNFalpha-stimulated stromal cells was examined with an enzyme-linked immunosorbent assay. The mRNA expression of HGF and its receptor c-Met in the stroma was investigated by RT-PCR. The localization of HGF and c-Met in isolated stromal cells and in intact tissue was examined by immunohistochemistry. The effect of HGF on the growth of stromal cells alone or in combination with IL-6 or TNFalpha was examined in a bromodeoxyuridine (BrdU) incorporation study. RESULTS: The production of HGF in the culture medium of stromal cells was significantly increased after single or combined treatment with either IL-6 or TNFalpha when compared with non-treated cells. The production of HGF by stromal cells derived from the eutopic endometrium of women with endometriosis was significantly higher than that of cells from women without endometriosis. This effect was paralleled by increased expression of HGF and c-Met mRNA, as demonstrated by RT-PCR. The BrdU incorporation study indicated that the addition of HGF enhanced the growth of endometrial and endometriotic stroma alone or in combination with IL-6 or TNFalpha. CONCLUSION: IL-6 and TNFalpha are involved in the production of HGF by endometrial stromal cells and may be involved in the growth of endometriosis by an autocrine mechanism.

Antimetabolites↗

PubMed2005

No association between HLA-DRB1 alleles and susceptibility to advanced stage endometriosis in a Korean population.

BACKGROUND: The aetiological factors of endometriosis still remain poorly understood. While there is growing evidence that genetic and immunological factors play important roles in the pathogenesis of the disease, HLA-DRB1 alleles have been reported to be associated with the risk of endometriosis in Japanese populations. This study was performed to determine whether susceptibility to advanced endometriosis is also associated with HLA-DRB1 alleles in a Korean population, which is the closest ethnic group to Japanese. METHODS: We recruited 100 Korean patients with advanced endometriosis confirmed by surgical and histolological examinations. HLA-DRB1 genotyping was carried out in two steps. Low to intermediate resolution typing was performed by PCR sequence-specific oligonucleotide hybridization method, followed by high resolution typing utilizing group-specific amplification and PCR-single strand conformation polymorphism method. Distribution of HLA-DRB1 alleles was compared with that of 800 unrelated ethnically matched individuals as well as 108 healthy female subjects. RESULTS: Genotyping revealed that the distribution of HLA-DRB1 alleles in patients with advanced endometriosis was not different from that in the two control groups. CONCLUSIONS: The findings of the present study suggest that susceptibility of advanced endometriosis is not associated with HLA-DRB1 alleles in a Korean population, which is apparently not the case in the Japanese population.

Adult↗

PubMed2006

Leukaemia inhibitory factor and interleukin 11 levels in uterine flushings of infertile patients with endometriosis.

BACKGROUND: Exact aetiology of infertility in stage I/II endometriosis patients is not known. Interleukin 11 (IL-11) and leukaemia-inhibitory factor (LIF) are factors associated with implantation window in human eutopic endometrium. We decided to test whether there is an altered secretion of these factors, which could explain receptivity defect in patients with minimal endometriosis. METHODS: Uterine flushing and endometrial samples were collected 7-9 days after ovulation (implantation window) from infertile patients with stage I/II endometriosis (n = 14) and fertile, endometriosis-free controls (n = 21). IL-11 and LIF were assessed in uterine flushings in eutopic endometria in all patients by enzyme-linked immunosorbent assay (ELISA). In eutopic endometrium, semiquantitative RT-PCR was performed for LIF and IL-11 mRNA expressions. RESULTS: No statistically significant differences were found in uterine flushing in women with and without endometriosis with regard to IL-11 levels (0.0 pg/ml versus 0.0 pg/ml) and LIF (25.53 pg/ml versus 36.26 pg/ml). These results were confirmed by the results of RT-PCR, where there were also no differences between studied groups. CONCLUSIONS: There is no receptivity defect with regard to LIF and IL-11 secretions by eutopic endometrium in infertile women with endometriosis.

Adult↗

PubMed2006

Endometriosis involving the ileocaecal junction with regional lymph node involvement in the baboon--striking pathological finding identical between the human and the baboon: a case report.

The baboon is an established model for endometriosis research. This report describes the occurrence of spontaneous endometriosis involving the ileocaecal junction and associated regional lymph nodes in the baboon. All endometriotic foci lacked the nuclear atypia, abnormal mitotic activity and altered nuclear-to-cytoplasmic ratio typical of malignancy. These findings are identical to reports in the human in which ileocaecal and colonic endometriosis is associated with endometriosis in pericolonic and mesenteric lymph nodes. The similarity between baboon and human colonic endometriosis in both location and pathology is striking and lends further evidence supporting the validity of the baboon as a model for human endometriosis.

Animals↗

PubMed2006

Effect of GnRH analogues on apoptosis and expression of Bcl-2, Bax, Fas and FasL proteins in endometrial epithelial cell cultures from patients with endometriosis and controls.

BACKGROUND: Our purpose was to evaluate the effect of the GnRH agonist (GnRHa), leuprolide acetate (LA), and the GnRH antagonist (GnRHant), Antide, on apoptosis and expression of apoptosis-related proteins in endometrial epithelial cell (EEC) cultures from patients with endometriosis and controls (infertile women without endometriosis). METHODS: Biopsy specimens of eutopic endometrium were obtained from 22 patients with endometriosis and from 14 women that served as controls. Apoptosis was examined in EEC after incubation with LA and Antide. Bax, Bcl-2, Fas and FasL expression was evaluated after exposure to LA, Antide or a combination of both. The percentage of apoptotic cells (%ApC) was assessed by the acridine orange-ethidium bromide technique, and protein expression was evaluated by western blot and immunocytochemistry. RESULTS: LA 100 and 1000 ng/ml increased the %ApC in EEC from patients with endometriosis (both P < 0.05) and controls (p < 0.05 and P < 0.01, respectively). Antide 10(-5) M increased the %ApC in EEC from patients with endometriosis and controls (P < 0.01). In EEC from women with endometriosis, Bax expression increased after treatment with LA, Antide and LA + Antide (P < 0.05, P < 0.001 and P < 0.001), whereas Bcl-2 expression decreased after exposure to LA and Antide (P < 0.001 and P < 0.01). FasL expression increased after LA, Antide and LA + Antide treatments (P < 0.01, P < 0.001 and P < 0.01). No significant changes were observed on Fas expression. CONCLUSIONS: GnRH analogues enhanced apoptosis in EEC, and this was accompanied by an increase in expression of the pro-apoptotic proteins Bax and FasL and a decrease in expression of the anti-apoptotic protein Bcl-2.

Apoptosis↗

PubMed2006

Deep dyspareunia and sex life after laparoscopic excision of endometriosis.

BACKGROUND: Among subjects with endometriosis and deep dyspareunia (DD), those with endometriosis of the uterosacral ligament (USLE) have the most severe impairment of sexual function. This study examines the effect of laparoscopic excision of endometriosis on DD and quality of sex life. METHODS: This observational cohort prospective study included 68 women with endometriosis suffering DD (intensity of pain >or= 6 on a 10-cm visual analogue scale). Patients underwent laparoscopic full excision of endometriosis. Following surgery, they were asked to use nonhormonal contraception devices. Before surgery, at 6- and at 12-month follow-up, patients answered a self-administered questionnaire based on the Sexual Satisfaction Subscale of the Derogatis Sexual Functioning Inventory. RESULTS: At 6- and 12-month follow-up, women with and without USLE had significant improvement in DD. Subjects with USLE reported increased variety in sex life, increased frequency of intercourse, more satisfying orgasms with sex, relaxing more easily during sex and being more relaxed and fulfilled after sex. Similar improvements were observed among women without USLE; however, for some variables statistical significance was not reached. CONCLUSIONS: Surgical excision of endometriosis improves not only DD but also the quality of sex life.

Adult↗

PubMedDate not supplied

Endometriosis: candidate genes.

Endometriosis is generally regarded as a benign disease but it does exhibit some characteristics reminiscent of malignancy. This raises the possibility that, like malignant diseases, the development of endometriosis may involve the acquisition of somatic genetic alterations in genes that regulate cell growth and differentiation. Studies over the past few years have substantiated this view with the identification of a variety of genetic abnormalities usually only associated with malignancies. Our own studies have shown that genetic alterations, as shown by loss of heterozygosity, are relatively common in endometriosis implying that tumour suppressor gene inactivation is likely to be involved in the proliferation and maintenance of all endometriotic implants. We have also shown by DNA fingerprinting that endometriotic lesions found adjacent to ovarian cancers have a common lineage, reinforcing the compelling histological and epidemiological data that endometriosis is a precursor of endometrioid and clear cell ovarian cancers. It is now well accepted that susceptibility to endometriosis may also involve an inherited genetic component. Studies aimed at identifying the predisposing genes are still in their infancy but should eventually provide invaluable insights into the pathology and aetiology of endometriosis.

DNA Fingerprinting↗

PubMed2005

Aromatase and other steroidogenic genes in endometriosis: translational aspects.

Endometriosis is a common, chronic and estrogen-dependent gynaecological disorder associated with pelvic pain and infertility. In addition to, or perhaps as a consequence of, immune, environmental and genetic factors, endometriotic lesions show high estradiol (E(2)) biosynthesis and low E(2) inactivation compared with normal endometrium. Current medical therapies of pain, which aim to lower circulating E(2) concentrations, are not effective in at least half of these patients. We and others recently demonstrated the expression of a few steroidogenic genes in endometriosis. The most important genes in this group are steroidogenic acute regulatory protein (StAR) and aromatase. Both are essential for E(2) production. Prostaglandin E(2) (PGE(2)) is the most potent known stimulator of both StAR and aromatase. PGE(2) production in endometriosis is up-regulated by increased levels of the enzyme cyclo-oxygenase-2 (COX-2) in this tissue. COX-2 in turn is stimulated by E(2), interleukin-1beta (IL-1beta) and PGE(2) itself in endometrial and endometriotic cells. Thus, there is a positive feedback loop that favours continuous formation of E(2) and PGE(2) in endometriosis. These basic findings led to recent phase-II studies employing aromatase inhibitors in the treatment of endometriosis. Aromatase inhibitors treat both postmenopausal and premenopausal endometriosis at least as effectively as the existing medical treatments. In premenopausal women, we and others administered aromatase inhibitors in combination with an ovarian-suppressant treatment. In this review, we emphasize the most recent basic studies in detail and provide a short summary of recent clinical trials.

Aromatase↗

PubMed2005

Endometrioid adenocarcinoma arising from endometriosis of the mesenterium of the sigmoid colon.

This report presents a case of endometrioid adenocarcinoma arising from endometriosis of the mesenterium of the sigmoid colon following total abdominal hysterectomy and bilateral salpingo-oophorectomy for leiomyoma of the uterus and infiltrating pelvic endometriosis, and hormone replacement therapy. A 62-year-old woman presented with an abdominal tumor. Based on the diagnosis of mesocolonic tumor, sigmoidectomy with lymph node resection was performed. The tumor cells were immunopositive for cytokeratin 7, but negative for cytokeratin 20, and the tumor was histologically diagnosed as endometrioid adenocarcinoma of the mesocolon. Hyperestrogenism has been implicated as a risk factor for the development of cancer from endometriosis. The patient had been receiving high-dose unopposed estrogens for 14 years after a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Physicians should recognize that endometriosis-associated neoplasms are able to cause symptoms or signs such as abdominal and/or pelvic pain, pelvic mass, and vaginal bleeding, especially if the patient has been treated with hormone replacement therapy. It is important to recognize the possibility of tumors arising from endometriosis when evaluating intestinal or mesenteric neoplasms in women, even in the patient who has previously undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy, particularly if the patient has a history of endometriosis and has received hormone replacement therapy.

Carcinoma, Endometrioid↗

PubMed1996

Endometriosis associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT).

To explore a possible connection between endometriosis, Müllerian anomalies, and possession of the N314D allele of the gene for galactose-1-phosphate uridyl transferase (GALT), we studied 33 women with endometriosis attending a fertility clinic. Patients completed questionnaires and had DNA tested for the N314D mutation of GALT. A previously completed general population survey of 111 women which obtained the same information was available for comparison. Women with endometriosis were more likely to carry at least one N314D allele (30% compared with 14%) and more likely to report a medical history of scoliosis (21% compared with 2%) compared to general population controls: two features we have described in women with vaginal agenesis. Compared with endometriosis cases without the N314D allele, those cases with the allele tended to have more advanced disease and a family history of endometriosis. We speculate that endometriosis may arise due to defects of canalization of the cervix leading to cervical stenosis and retrograde menstruation. The relevance of the N314D mutation, via this model, may derive from an association between abnormalities of galactose metabolism and vaginal agenesis which represents a canalization defect of the vaginal plate of the Müllerian tubercle, the same structure which gives rise to the cervix.

Contraceptives, Postcoital, Synthetic↗

PubMed2000

Increased concentrations of secretory leukocyte protease inhibitor in peritoneal fluid of women with endometriosis.

Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. We investigated whether SLPI was present in the peritoneal fluid of women with endometriosis and to clarify the role of SLPI in the pathogenesis of endometriosis. Western blot analyses revealed that SLPI protein was detected as a 12 kDa band in peritoneal fluid. The peritoneal fluid concentrations of SLPI, elastase and interleukin-6 were assayed by enzyme-linked immunosorbent assays (ELISA). SLPI concentrations and the SLPI/elastase ratio in the peritoneal fluid of women with endometriosis were higher than in samples from women without endometriosis. There was no significant correlation between concentrations of SLPI and interleukin-6 in the peritoneal fluid. Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive staining in peritoneal macrophages, but not lymphocytes. The present findings suggest that SLPI found in the peritoneal fluid of patients with endometriosis may contribute to the pathogenesis of endometriosis.

Adult↗

PubMed2004

Analysis of the involvement of CCR5-Delta32 and CCR2-V64I variants in the development of endometriosis.

Several arguments support the proposal that the cytokine network plays a critical role in the aetiology of endometriosis. Among various chemokines, regulated-on-activation, normal-T-cell-expressed and -secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1) concentrations have been shown to be increased in the peritoneal fluid of women with endometriosis. Some studies have demonstrated that, in the context of endometriosis, these chemokines are involved in apoptosis, angiogenesis and/or chemotaxis. Since the chemokines exert their effects by binding to their receptors, it would be plausible that factors affecting such interactions might play a role in the pathogenesis of endometriosis. Thus we postulated that the genes encoding CCR5 and CCR2, which are the receptors for RANTES and MCP-1 respectively, could be good candidate genes for the disease. We have used real-time PCR and FRET technologies to genotype and evaluate the variants CCR5-Delta32 and CCR2-V64I, as susceptibility factors in a cohort of Spanish women with endometriosis. No differences have been found in the frequencies of the two polymorphisms nor in the haplotype/genotype distribution between cases and controls. These data would suggest the lack of association between these polymorphisms and endometriosis in our population, although they do not permit us to discard completely a possible role of other variants within CCR5 and CCR2 genes in this pathology.

Endometriosis↗

PubMed2004

Glutathione S-transferase M1*null genotype but not myeloperoxidase promoter G-463A polymorphism is associated with higher susceptibility to endometriosis.

Glutathione S-transferase M1 (GSTM1), one member of the GST family, is responsible for metabolism of xenobiotics and carcinogens. Myeloperoxidase (MPO) plays an important role in the oxidation and activation of carcinogens and nitric oxide. Allelic variants of GSTM1 and MPO gene polymorphisms might impair detoxification function and increase the susceptibility to endometriosis. We aimed to investigate if these polymorphisms are useful markers for predicting endometriosis susceptibility. Women were divided into two groups: (i) endometriosis (n=150); (ii) non-endometriosis (n=159). Polymorphisms for GSTM1 and MPO were amplified by polymerase chain reaction and detected by electrophoresis after restriction digestion. The relative frequencies of the GSTM1*wild (+/+,+/0)/null (0/0) genotypes and MPO-463*G/A gene polymorphisms between both groups were compared. The distribution of GSTM1 polymorphisms was significantly different between the two groups. Proportions of GSTM1*wild/null alleles in both groups were: (i) 36.7/63.3%; (ii) 95/5% (P=0.001). In contrast, MPO-463 genotypes were not significantly different between the two groups. Proportions of MPO*A homozygote/heterozygote/G homozygote in both groups were: (i) 2.7/17.4/79.9% and (ii) 1.9/17/81.1% (P> 0.05). We conclude that the GSTM1*null genotype is associated with a higher risk of endometriosis development. MPO-463*G/A gene polymorphism is not related to the susceptibility of endometriosis.

Endometriosis↗