Uncovering moderators of pain perception by women with endometriosis from Latin America and Spain: the roles of sociodemographics, racial self-identity, and pain catastrophizing.

ABSTRACT: A cross-sectional multinational collaborative study on women with endometriosis from Latin America and Spain uncovered high levels of painful symptomatology and high pain catastrophizing scores. Associations between pain perception/catastrophizing and race/ethnicity have been documented. This study was conducted to uncover factors moderating pelvic pain severity, including socioeconomic variables, self-identified race, and pain catastrophizing in women with endometriosis from Latin America and Spain, a population encompassing diverse racial and sociocultural contexts. Self-reported data on demographics, clinical history, Ob-Gyn history, pelvic pain intensity, and pain catastrophizing were collected with the Spanish World Endometriosis Research Foundation (WERF) Endometriosis Phenome Project (EPhect) Clinical Questionnaire (ECQ). Multiple logistic regression was conducted to analyze effects of self-identified race, demographic clusters (defined as countries with similar racial population distribution), socioeconomic factors, and pain catastrophizing on reporting severe vs moderate-mild levels of dysmenorrhea, dyspareunia, and pelvic pain. Self-identified race did not affect the likelihood of reporting severe pelvic pain; however, there were significant differences in reporting severe dysmenorrhea at worst among demographic clusters. Older age was associated with severe dyspareunia at worst and recent pelvic pain. Pain catastrophizing score was highly predictive of reporting most types of severe pelvic pain, regardless of race and demographic cluster. These results negate a role of racial categories as moderator of pain in women from Latin America and Spain and support integration of pain catastrophizing assessments and psychological interventions into the pain management plan to enhance therapeutic outcomes and QoL for patients with endometriosis.

Racial disparities in uterine fibroids and endometriosis: a systematic review and application of social, structural, and political context.

IMPORTANCE: Uterine fibroids and endometriosis are 2 of the leading causes of morbidity among reproductive-aged women. There are significant racial disparities in disease prevalence, incidence, age of onset, and treatment profile in fibroids. The data on endometriosis are less clear. OBJECTIVE: To conduct a systematic review of racial disparities in prevalence of uterine fibroids and endometriosis in the United States and summarize the literature on these 2 highly prevalent benign gynecologic conditions using a framework that explicitly incorporates and acknowledges the social, structural, and political contexts as a root cause of racial disparities between Black and White women. EVIDENCE REVIEW: A systematic review regarding racial disparities in prevalence of fibroids and endometriosis was conducted separately. Two separate searches were conducted in PubMed to identify relevant original research manuscripts and prior systematic reviews regarding racial disparities in uterine fibroids and endometriosis using standardized search terms. In addition, we conducted a structured literature search to provide social, structural, and political context of the disparities. FINDINGS: A systematic review of the literature indicated that the prevalence of uterine fibroids was consistently higher in Black than in White women with the magnitude of the difference varying depending on population and case definition. Prevalence of endometriosis varied considerably depending on the base population and case definition, but was the same or lower among Black vs. White women. As a result of the social, structural, and political context in the United States, Black women disproportionately experience a range of exposures across the life course that may contribute to their increased uterine fibroid incidence, prevalence, and severity of uterine fibroids. However, data suggest no racial difference in the incidence of endometriosis. Nevertheless, Black women with fibroids or endometriosis experience worse clinical and surgical outcomes than their White counterparts. CONCLUSION AND RELEVANCE: Racial disparities in uterine fibroids and endometriosis can be linked with differential exposures to suspected etiologic agents, lack of adequate access to health care, including highly skilled gynecologic surgeons, and bias and discrimination within the health care system. Eliminating these racial disparities will require solutions that address root causes of health disparities through policy, education and programs to ensure that all patients receive culturally- and structurally-competent care.

Frequent DYSF rare variants/mutations in 152 Han Chinese samples with ovarian endometriosis.

PURPOSE: Endometriosis is a common chronic gynecological disease greatly affecting women health. Prior studies have implicated that dysferlin (DYSF) aberration might be involved in the pathogenesis of ovarian endometriosis. In the present study, we explore the potential presence of DYSF mutations in a total of 152 Han Chinese samples with ovarian endometriosis. METHODS: We analyze the potential presence of DYSF mutations by direct DNA sequencing. RESULTS: A total of seven rare variants/mutations in the DYSF gene in 10 out of 152 samples (6.6%) were identified, including 5 rare variants and 2 novel mutations. For the 5 rare variants, p.R334W and p.G941S existed in 2 samples, p.R865W, p.R1173H and p.G1531S existed in single sample, respectively; for the two novel mutations, p.W352* and p.I1642F, they were identified in three patients. These rare variants/mutations were absent or existed at extremely low frequency either in our 1006 local control women without endometriosis, or in the China Metabolic Analytics Project (ChinaMAP) and Genome Aggregation Database (gnomAD) databases. Evolutionary conservation analysis results suggested that all of these rare variants/mutations were evolutionarily conserved among 11 vertebrate species from Human to Fox. Furthermore, in silico analysis results suggested these rare variants/mutations were disease-causing. Nevertheless, we find no significant association between DYSF rare variants/mutations and the clinical features in our patients. To our knowledge, this is the first report revealing frequent DYSF mutations in ovarian endometriosis. CONCLUSION: We identified a high frequency of DYSF rare variants/mutations in ovarian endometriosis for the first time. This study suggests a new correlation between DYSF rare variants/mutations and ovarian endometriosis, implicating DYSF rare variants/mutations might be positively involved in the pathogenesis of ovarian endometriosis.

The expression and significance of leukemia inhibitory factor, interleukin-6 and vascular endothelial growth factor in Chinese patients with endometriosis.

OBJECTIVE: To observe the levels of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in blood, peritoneal fluid, ectopic endometrial tissue, and ectopic endometrial stromal cells of patients with endometriosis, and to compare expression of IL-6, LIF and VEGF expression between endometriotic and non-endometriotic patients underwent laparoscopic surgery. METHODS: Thirty-one patients who underwent laparoscopic surgery for endometriosis in our hospital from January 2018 to January 2020 were included in the observation group, and 32 patients who underwent laparoscopic surgery for uterine fibroids, ovarian serous cystadenoma, and ovarian teratomas, were included in the control group. The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the two groups of patients were detected. The levels of LIF, IL-6 and VEGF in ectopic endometrial tissue and self-paired eutopic endometrial tissue, ectopic endometrial stromal cells and self-paired eutopic endometrial stromal cells of patients in the observation group were detected. After treating the primary cultured ectopic endometrial stromal cells with LIF and IL-6 alone or in combination, the changes of VEGF mRNA of ectopic endometrial stromal cells and the VEGF levels in the supernatant were observed. RESULTS: The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the observation group were all higher than those of the control group (P < 0.05), and the levels of LIF, IL-6 and VEGF in the peritoneal fluid of the observation group were significantly higher than those in the blood (P < 0.05). In the observation group, the expression levels of LIF-mRNA and IL-6 mRNA in the ectopic endometrial tissue were higher than those in the self-paired eutopic endometrial tissues (P < 0.05), while the expression level of VEGF mRNA in the ectopic endometrial tissues was lower than that in the self-paired eutopic endometrial tissues (P < 0.05). Besides, the mRNA expression levels of LIF, IL-6 and VEGF in ectopic endometrial stromal cells of the observation group were all higher than those in the self-paired eutopic endometrial stromal cells (P < 0.05). After stimulating ectopic endometrial stromal cells with LIF, IL-6 and LIF + IL-6, respectively, the VEGF levels in the supernatant were all significantly higher than that in the blank control group (P < 0.05). CONCLUSION: The LIF, IL-6 and VEGF levels in blood and peritoneal fluid were increased in patients with endometriosis, and increased LIF and IL-6 in ectopic endometriosis stromal cells can play a synergistic role in increasing the VEGF levels, which may be involved in the occurrence and development of endometriosis.

Inhibitory KIR2DL2 Gene: Risk for Deep Endometriosis in Euro-descendants.

Endometriosis (EDT) is an inflammatory disease characterized by implantation/growth of endometrial tissue, glands, and/or stroma, outside the uterus. Reduced NK cell cytotoxic activity has been implicated in its pathogenesis, together with other immunologic alterations. We investigated the influence of KIR gene polymorphisms and their HLA ligand combinations in deep endometriosis (DE) susceptibility. One hundred sixty women with a histological diagnosis of DE and 202 control women without the disease, who underwent laparoscopy, were enrolled. The DE group was subdivided into initial (I/II; n = 60) and advanced stages (III/IV, n = 100). KIR and HLA class I gene polymorphisms were typed by PCR-SSP and sequence-based-typing (SBT), respectively. We observed a significant association of KIR2DL2, an inhibitory gene of B haplotype, conferring risk for DE in Euro-descendants. Positive associations of Bx haplotype and centromeric AB segments were also found. However, no association with KIR-HLA ligand combination was observed. Our data suggest KIR2DL2 gene to be a relevant factor favoring NK inhibition in DE in Euro-descendants, contributing to the defective NK cytotoxic activity and impaired clearance of ectopic endometrial cells in the disease.

Influence of race/ethnicity on prevalence and presentation of endometriosis: a systematic review and meta-analysis.

BACKGROUND: Understanding the impact of race/ethnicity on the prevalence and presentation of endometriosis may help improve patient care. OBJECTIVE: To review systematically the evidence for the influence of race/ethnicity on the prevalence of endometriosis. SEARCH STRATEGY: CENTRAL, MEDLINE, PubMed, Embase, LILACS, SCIELO, and CINAHL databases, as well as the grey literature, were searched from date of inception until September 2017. SELECTION CRITERIA: Randomised control trials and observational studies reporting on prevalence and/or clinical presentation of endometriosis. DATA COLLECTION AND ANALYSIS: Twenty studies were included in the review and 18 studies were used to calculate odds ratio (OR) with 95% confidence interval (CI) through a random effects model. Methodological quality was assessed using the Newcastle-Ottawa risk of bias scale (NOS). MAIN RESULTS: Compared with White women, Black woman were less likely to be diagnosed with endometriosis (OR 0.49, 95% CI 0.29-0.83), whereas Asian women were more likely to have this diagnosis (OR 1.63, 95% CI 1.03-2.58). Compared with White women, there was a statistically significant difference in likelihood of endometriosis diagnosis in Hispanic women (OR 0.46, 95% CI 0.14-1.50). Significant heterogeneity (I2  > 50%) was present in the analysis for all racial/ethnic groups but was partially reduced in subgroup analysis by clinical presentation, particularly when endometriosis was diagnosed as self-reported, CONCLUSIONS: Prevalence of endometriosis appears to be influenced by race/ethnicity. Most notably, Black women appear less likely to be diagnosed with endometriosis compared with White women. There is scarce literature exploring the influence of race/ethnicity on symptomatology, as well as treatment access, preference, and response. TWEETABLE ABSTRACT: Prevalence of endometriosis may be influenced by race/ethnicity, but there is limited quality literature exploring this topic.

Behind the times: revisiting endometriosis and race.

Endometriosis is a common gynecologic condition, affecting approximately 10% of reproductive-aged women. It commonly presents with pelvic pain, painful periods, and infertility and can significantly have an impact on one's quality of life. Early exploration into the pathophysiology of this condition identified race as a risk factor for endometriosis, with the condition predominantly identified in white women. It is still unclear whether there is a biological basis for this conviction or whether it can be explained by methodological and social bias that existed in the literature at that time. Although there is more recent literature exploring the association between endometriosis and race/ethnicity, studies have continued to focus on the prevalence of disease and have not taken into account possible variation in disease presentation among women of different ethnicities. Furthermore, information on diverse populations by race/ethnicity, other than white or black, is quite limited. This paper explores the history of how the association between endometriosis and whiteness was established and whether we still ascribe to a certain stereotype of a typical endometriosis patient today. Furthermore, we discuss the potential implications of such a racial bias on patient care and suggest areas of focus to achieve a personalized and patient focused approach in endometriosis care.

East and South East Asian Ethnicity and Moderate-to-Severe Endometriosis.

STUDY OBJECTIVE: To investigate ethnic differences for moderate-to-severe endometriosis. DESIGN: Analysis of a prospective registry (Canadian Task Force classification II-2). SETTING: Tertiary referral center. PATIENTS: A total of 1594 women with pelvic pain and/or endometriosis. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: On logistic regression, adjusting for potential confounders, East/South East Asians were 8.3 times more likely than whites to have a previous diagnosis of stage III/IV endometriosis before referral (adjusted odds ratio [aOR], 8.33; 95% confidence interval [CI], 3.74-18.57), 2.7 times more likely to have a palpable nodule (aOR, 2.66; 95% CI, 1.57-4.52), 4.1 times more likely to have an endometrioma on ultrasound (aOR, 4.10; 95% CI, 2.68-6.26), and 10.9 times more likely to have stage III/IV endometriosis at the time of surgery at our center (aOR, 10.87; 95% CI, 4.34-27.21). CONCLUSION: Moderate-to-severe endometriosis was more common in women with East or South East Asian ethnicity in our tertiary referral center.  This could be explained by East/South East Asians with minimal to mild disease being less likely to seek care or genetic/environmental differences that increase the risk of more severe disease among East/South East Asians. (ClinicalTrials.gov, NCT02911090.).

Dienogest for Treatment of Endometriosis in Chinese Women: A Placebo-Controlled, Randomized, Double-Blind Phase 3 Study.

BACKGROUND: Dienogest is a progestin with demonstrated efficacy in the treatment of endometriosis in European women. The objective of this study was to evaluate the efficacy and safety of dienogest in Chinese women. PATIENTS AND METHODS: This 24-week, randomized, double-blind, placebo-controlled multicenter (n = 23) study evaluated the efficacy and safety of 2 mg dienogest once daily in 255 Chinese women aged 18-45 years with laparoscopically diagnosed endometriosis and an endometriosis-associated pelvic pain (EAPP) score ≥30 mm on a 0-100 mm visual analog scale. The primary efficacy variable was absolute change in EAPP from baseline to week 24. Secondary efficacy variables included proportions of responders and intake of supportive analgesic medication. Safety variables included adverse events (AEs), laboratory parameters, and bleeding patterns. Bone mineral density (BMD) was evaluated in a subset of 140 women. RESULTS: After 24 weeks of treatment, the difference between treatment arms for mean reduction in EAPP was statistically significant in favor of dienogest (-24.54 mm; 95% CI -29.93 to -19.15; p < 0.0001). Secondary efficacy analyses supported the significant superiority of dienogest over placebo. Dienogest was well tolerated, with few AEs associated with therapy. Dienogest had no effect on BMD levels after 24 weeks of treatment. CONCLUSIONS: Dienogest 2 mg once daily for 24 weeks was superior to placebo in reducing EAPP and was safe and well tolerated in Chinese women with endometriosis. The results are consistent with studies previously conducted in European women.

[Risk factors of endometriosis associated ovarian carcinoma in women aged 45 years and older].

Obiective: To explore the risk factors of endometriosis-associated ovarian cancer (EAOC) in women with ovarian endometriosis aged 45 years and older in China. Methods: The medical records of total 1 038 women aged 45 years and older with a surgicopathological diagnosis of ovarian endometriosis treated at Peking Union Medical College Hospital from December 1994 to December 2014 were reviewed. Histology evaluation determined ovarian endometriosis with (n=30) or without (n=1 008) ovarian cancer. Results: (1) There were 30 (2.9%, 30/1 018) cases confirmed as having EAOC. Clear cell carcinoma (63.3%, 17/30) and endometrioid adenocarcinoma (23.3%, 7/30) were commonly observed subtypes and 70.0% of EAOC patients were at stage Ⅰ. (2) Compared women with ovarian endometriosis in the same age group, patients with EAOC were older (50.8 vs 48.5 years, P=0.002). There were more in postmenopausal status at diagnosis of EAOC (P<0.01). There were more found with a mass ≥8 cm (P<0.01). Women with EAOC had higher prevalence of coexisting endometrial disorders (P=0.003). No differences were found in preoperative CA(125) value and infertile or nulliparous women (P>0.05). Conclusions: For women with ovarian endometriosis aged 45 years and older, the subgroup of patients characterized by postmenopausal status and ovarian endometrioma (≥8 cm) have a higher risk of EAOC. Active intervention or intensive follow-up should be considered for this population group, especially for those concurrent with endometrial disorders.

Association of two selected polymorphisms with developed endometriosis in women from Slovakia.

OBJECTIVES: To clarify the connection between two selected mononucleotide polymorphisms (rs4957014 and rs3756712) in programmed cell death gene 6 (PDCD6) and endometriosis development risk in patients belonging to the majority population of Slovakia. METHODS: From all women involved in the research a buccal DNA sample was taken. A genetic analysis of selected polymorphisms was implemented using Real-time PCR method. Variance in allelic and genotype frequencies was statistically evaluated between the controlgroup and the group of patients. RESULTS: The analysed group consisted of 52 women suffering from endometriosis and the control group of 63 women. Variant G allele frequency in the group of patients in case of polymorphism rs3756712 had a value of 0.42 and in the control group 0.29; that represents its statistically and significantly higher occurrence in the group of patients suffering from endometriosis (p = 0.029 and OR = 1.833). Presence of G allele is related to almost 1.9 times higher risk of endometriosis development. CONCLUSION: Achieved results show that polymorphism rs3756712 is significantly associated with the risk of endometriosis development in Slovak women. Polymorphism rs4957014 did not show any connection with development of endometriosis (Tab. 5, Ref. 10).

p53 Arg72Pro polymorphism confers the susceptibility to endometriosis among Asian and Caucasian populations.

PURPOSE: Findings from studies on the association between the p53 Arg72Pro polymorphism and endometriosis susceptibility have so far been inconsistent. Therefore, we undertook a meta-analysis to clarify the association of p53 Arg72Pro polymorphism with the risk of endometriosis. METHODS: Relevant studies were chosen by searching PubMed, Embase, the Cochrane Library databases, CNKI, Wanfang database, and CBM for articles published before and up to April 30, 2015. Two independent reviewers performed the eligibility evaluation and data extraction. The odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for the overall risk estimate. RESULTS: Eleven case-control studies involving 1834 endometriosis cases and 2331 controls were included. Pooled data analysis suggested that the p53 72Pro variant is a significant endometriosis risk factors in comparison to the 72Arg variant (Pro vs. Arg: OR = 1.298, 95 % CI 1.082-1.558; Pro/Pro vs. Arg/Arg: OR = 1.751, 95 % CI 1.130-2.711; Pro/Arg vs. Arg/Arg: OR = 1.530, 95 % CI 1.174-1.994), which was strengthened in the dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 1.570, 95 % CI = 1.181-2.087). In the stratified analysis by ethnicity and Hardy-Weinberg equilibrium (HWE) in the controls, we found strong associations in Asians and in studies that were consistent with HWE. However, the analyses of the revised American Fertility Society (rAFS) stage and the menopausal status subgroup did not reveal any significant associations. CONCLUSION: In conclusion, the p53 Arg72Pro polymorphism was closely related to the risk of endometriosis, especially in Asian populations.

Evaluation of the frequency of G-765C polymorphism in the promoter region of the COX-2 gene and its correlation with the expression of this gene in the endometrium of women with endometriosis.

OBJECTIVE: To evaluate the frequency of polymorphism G-765C (rs20417) of the COX-2 gene and the expression of this gene in the endometrium of women with endometriosis. STUDY DESIGN: This is a case-control study of 365 women with endometriosis (251 infertile and 114 fertile) submitted to laparoscopy/laparotomy with histological confirmation of endometriosis. The control group was composed of 522 fertile women without endometriosis. Of these, 37 patients from the endometriosis group and 47 from the control group were submitted to biopsy of the endometrium for analysis of the expression of the COX-2 gene. The genotypes were determined using analysis by High-Resolution Melt. Gene expression was measured by qRT-PCR with TaqMan methodology using the GAPDH gene as normalizer of the reactions. RESULTS: The distribution of the genotypes and alleles in the group of fertile women with moderate/severe endometriosis showed a statistically significant difference, demonstrating association of the ancestral allele, -765G, with increased risk of endometriosis (p = 0.028; OR 0.53; CI 0.32-0.90). The mean expression of the COX-2 gene (mRNA PTGS2) in the group of women with endometriosis was statistically higher compared to the control group (3.85 versus 2.84, p = 0.028). CONCLUSION: The present study identified that in Brazilian women the presence of the ancestral allele, -765G, of the COX-2 gene is associated with an increased risk for development of moderate/severe endometriosis associated with fertility, and that the eutopic endometrium of women with endometriosis showed increased expression of COX-2 when compared to the control group.

TP53 Arg72Pro polymorphism (rs1042522) and risk of endometriosis among Asian and Caucasian populations.

This study was conducted to investigate the association between TP53 Arg72Pro polymorphism (rs1042522) and risk of endometriosis. Studies were retrieved from Pubmed, Embase and HuGENet, and four models [dominant (AA+AG vs. GG), recessive (AA vs. AG+GG), co-dominant (AA vs. AG, AA vs. GG) and allele analysis (A vs. G), combined with odds ratios (OR) and 95% confidence intervals (CI)], were applied to evaluate this association. Fourteen eligible studies from eight countries were included. The pooled analysis identified a significant association between TP53 Arg72Pro polymorphism (rs1042522) and risk of endometriosis [dominant: OR 0.746, 95% CI 0.585-0.952, I(2)=59%; recessive: OR 0.650, 95% CI 0.510-0.829, I(2)=73%; co-dominant (GG vs. GC): OR 0.676, 95% CI 0.637-0.851, I(2)=67%; co-dominant (GG vs. CC): OR 0.564, 95% CI 0.395-0.806, I(2)=74%; allele analysis: OR 0.762, 95% CI 0.654-0.888, I(2)=71%]. In the subgroup analysis, the same positive associations were found among Asians. After removing studies that did not satisfy Hardy-Weinberg equilibrium, significant correlations were confirmed in both the pooled analysis and the Asian subgroup. Three bioinformatic methods (TagSNP calculations, functional prediction and linkage disequilibrium analysis) were used to determine the importance of TP53 Arg72Pro polymorphism (rs1042522), and suggested that this locus may be equally important regardless of ethnicity. In conclusion, TP53 Arg72Pro polymorphism (rs1042522) was positively associated with risk of endometriosis, particularly among Asians. However, its potential role in Caucasians should not be ignored.

Meta-analysis of association between the TP53 Arg72Pro polymorphism and risk of endometriosis based on case-control studies.

OBJECTIVE: In the light of the relationship between the TP53 Arg72Pro (rs1042522) polymorphism and the risk of endometriosis remains inclusive or controversial. For better understanding of the effect of TP53 Arg72Pro polymorphism on endometriosis risk, we performed a meta-analysis. METHODS: The relevant studies were identified through a search of PubMed, Web of Science, EMBASE, Ovid, Springer, China National Knowledge Infrastructure (CNKI), cqvip, Wanfang database, and Chinese Biomedical Literature (CBM) databases up to December, 2014. The association between the TP53 Arg72Pro polymorphism and endometriosis risk was pooled by conducted by odds ratios and 95% confidence intervals. RESULTS: A total of fifteen case-control studies with 2683 cases and 3335 controls were eventually identified. There was significant association between Arg72Pro polymorphism and endometriosis risk in all of the five models in overall populations (C vs. G: OR=1.32, 95%CI=1.14-1.53, p=0.00; CC vs. GG: OR=1.80, 95%CI=1.28-2.53, p=0.001; GC vs. GG: OR=1.52, 95%CI=1.22-1.88, p=0.00; CC vs. GC/GG: OR=1.32, 95%CI=1.05-1.66, p=0.016; CC/GC vs. GG: OR=1.59, 95%CI=1.26-2.00, p=0.00). In the sub-group analysis according to ethnicity, the results suggested that TP53 Arg72Pro polymorphism was not associated with endometriosis risk in Caucasians. However, the significant association was found in Asians and Mixed race (MIX) under the five models. CONCLUSIONS: The results of this meta-analysis suggest that the TP53 Arg72Pro polymorphism can increase the risk of endometriosis, especially among Asians and MIX populations. Considering the limited sample size and ethnicities included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results.

Association between genetic variants of the VEGFR-2 gene and the risk of developing endometriosis in Northern Chinese Women.

AIM: To investigate the association of tag single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor receptor 2 (VEGFR-2) gene with susceptibility to endometriosis. METHODS: This study comprised 571 patients with endometriosis and 580 women in the control group. Five tag SNPs in the VEGFR-2 gene were selected using a Haploview program, and those SNPs were genotyped by a method of polymerase chain reaction and ligase detection reaction. RESULTS: Statistical results show that there was a significant difference in the genotype and allele distribution of the 1192C/T polymorphism between the disease group and the control group (p = 0.041 and 0.017). The women carrying the T allele (C/T+T/T genotype) had a lower risk of developing endometriosis compared with the women with the C/C genotype (OR 0.75, 95% CI 0.57-0.99). There was no significant difference in the allele and genotype distribution of four other tag SNPs (1719T/A, +31C/T, IVS25-92A/G and IVS6+​54C/T) between the disease group and the control group (all p > 0.05). CONCLUSIONS: Our results suggested that the 1192C/T polymorphisms on the VEGFR-2 gene might affect the risk of developing endometriosis in Northern Chinese women of Han ethnicity.

A microRNA-520 mirSNP at the MMP2 gene influences susceptibility to endometriosis in Chinese women.

The MMP2 gene has been implicated in the pathogenesis of endometriosis. We investigated the role and function of single-nucleotide polymorphisms (SNP) of MMP2 in relation to endometriosis. First a case-control study was conducted and 17 SNPs were examined in 211 patients and 344 controls. Regression analysis was used to evaluate the genetic effect. We used reporter assay to validate the functional consequences of the significant SNP. Two SNPs (rs243832 and rs7201) had P-values <0.05 and they are in strong linkage disequilibrium (D'=0.96 and r(2)=0.47). Further analysis showed that rs7201 but not rs246832 was an independent risk factor and the risk C allele of rs7201 had an odds ratio (OR) of 1.88 (P=0.004). SNP rs7201 is located at the 3'-untranslated region and is predicted to be within the microRNA-520g binding site. The reporter assay for rs7201 showed that the risk C allele had a higher expression level than the A allele (P=0.027). Using microRNA-520g mimic and inhibitor, the results indicated that the A allele but not the risk C allele can be regulated by microRNA-520g. The C allele of SNP rs7201 increases a risk for endometriosis because of out of regulation by microRNA-520g.

Screening of a panel of steroid-related genes showed polymorphisms of aromatase genes confer susceptibility to advanced stage endometriosis in the Taiwanese Han population.

OBJECTIVE: To establish a multilocus model for studying the effect of steroid-related genes on advanced stage endometriosis. MATERIALS AND METHODS: A total of 121 patients with advanced stage endometriosis and 171 control women were included. Eighteen single-nucleotide polymorphisms (SNPs) from nine genes (HSD17B1, HSD17B2, HSD17B5, HSD17B6, CYP17, CYP19, ERα, ERß, and PGR) were genotyped using the TaqMan assays. Logistic regression models were used to evaluate the genetic effects, with adjustment for other covariates. RESULTS: Only the presence of the mutant CYP19 (aromatase gene) was associated with a significantly increased risk of endometriosis after adjusting for age, BMI, and parity (p = 0.002, OR = 2.69; 95% CI = 1.44-5.02). No association was ascertained between the other investigated SNPs and endometriosis. CONCLUSION: Polymorphisms of the aromatase gene confer susceptibility to advanced stage endometriosis in the Taiwanese Han population.

Translation and psychometric evaluation of the simplified Chinese-version Endometriosis Health Profile-30.

STUDY QUESTION: What are the psychometric properties in mainland China of the 30-item Endometriosis Health Profile (EHP-30) translated into simplified Chinese? SUMMARY ANSWER: The simplified Chinese version of the EHP-30 is a valid, reliable and acceptable tool for the measurement of the health-related quality of life (HRQoL) of women with endometriosis in the context of mainland China. WHAT IS KNOWN ALREADY: Endometriosis can critically affect women's HRQoL. The EHP-30 is currently the most reliable instrument to measure the HRQoL in women with endometriosis. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was conducted in a tertiary referral university hospital from February 2012 to August 2012 in Beijing, P. R. China. PARTICIPANTS/MATERIALS, SETTING, METHODS: The translation and cultural adaptation of the EHP-30 was performed according to accepted guidelines. The study included 336 women with endometriosis. Psychometric evaluation included factor analysis, convergent validity, measurement of internal consistency, item-total correlations and data completeness, descriptive statistics, and the determination of floor and ceiling effects. MAIN RESULTS AND THE ROLE OF CHANCE: Factor analysis confirmed the validity of the five-factor structure of the EHP-30 core questionnaire, which explained 79.51% of the total variance. The correlations of related subscale scores between EHP-30 and Short Form-36 were all significant. Cronbach's α for internal consistency across each scale ranged 0.89-0.97 for the core questionnaire and 0.80-0.96 for the modular questionnaire. No <97.67% of data completeness was achieved. Floor effects were observed in three scales: self-image (19.64%), children (26.67%) and medical profession (15.19%). No ceiling effects were found. The control and powerlessness scale had the highest median score (54.17) in the core questionnaire, whereas the infertility module (median = 56.25) had the highest score in the modular section. LIMITATIONS, REASONS FOR CAUTION: The study was conducted in a referral centre for the treatment of endometriosis, thereby leading to overrepresentation of severe symptoms of endometriosis. Furthermore, the test-retest reliability and responsiveness of the questionnaire were not evaluated in this study. WIDER IMPLICATIONS OF THE FINDINGS: Our study addresses the urgent need for a valid and reliable instrument to measure the HRQoL of female patients with endometriosis in mainland China. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants to J. Leng from the Key Project for Clinical Faculty Foundation, Ministry of Health, China (2010). None of the authors has any conflict of interest to declare.