Progesterone Receptor Gene Polymorphism Research Articles

PROGESTERONE RECEPTOR GENE POLYMORPHISM AS A FACTOR IN PRETERM BIRTH (LITERATURE REVIEW)

The purpose of the work – to analyze data from the world literature regarding thedetermination of the probable role of the progesterone receptor gene polymorphism asa factor in the occurrence of premature birth.Conclusions. 1. Progesterone receptor gene polymorphism plays a significant role inthe mechanisms of development and course of miscarriage, negative pregnancy outcomeand low birth weight of newborns. 2. The probability of the threat of premature birthin different periods of gestation or termination of pregnancy with premature birth maydepend on the presence of one or another polymorphism. 3. Genetic variability thatcan lead to changes in the biological functions of the progesterone receptor, the geneticpolymorphism of the progesterone receptor is a major risk factor for complications ofpreterm birth.

Type B Progesterone Receptor Polymorphism Increases the Risk of Pelvic Organ Prolapse in Balinese Women

This study aims to determine the role of type B progesterone receptor gene polymorphisms as a risk factor for pelvic organ prolapse in Balinese women. This paired case-control study involves 29 patients with pelvic organ prolapse as the case group and 29 patients without pelvic organ prolapse as the control group. The study was conducted at Sanglah Hospital, Denpasar and the Integrated Biomedical Laboratory, Faculty of Medicine, Udayana University. Three milliliters of venous blood samples were taken from each patient and PCR examination was performed to determine the type b progesterone receptor gene polymorphisms. Risk assessment of the type b progesterone receptor gene polymorphism for pelvic organ prolapse was done by controlling for confounding variables, including age, parity, body mass index, occupation, menopausal status, and history of hysterectomy, through multiple logistic regression tests. The type b progesterone receptor gene polymorphism increased the risk of pelvic organ prolapse three times compared to non-prolapsed in Balinese women (OR 3.90, 95%CI 1.16-13.07, p = 0.023). After controlling for various confounding variables, type b progesterone receptor gene polymorphism still increased the risk of pelvic organ prolapse up to four times (AOR 4.54, 95%CI 1.16-17.68, p = 0.029). The type b progesterone receptor gene polymorphism significantly increases the risk of pelvic organ prolapse in Balinese women.

POLYMORPHISMS OF THE PROGESTERONE RECEPTOR GENE IN ENDOMETRIOSIS PATIENTS OF SOUTH SUMATRA, INDONESIA

Polymorphisms of the progesterone receptor gene alter the expressions of two receptor isoforms involved in the regulation of progesterone's antiproliferative effect in endometriotic tissue. This study aims to identify the +331G/A polymorphism of the progesterone receptor gene in endometriosis patients in Palembang, South Sumatra. Identification of +331G/A single-nucleotide polymorphism (SNP) was conducted on 42 endometriosis patients through polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). In this study, twenty-six (61.9%) subjects had heterozygous mutant genotype for the +331G/A SNP. No subject with homozygous mutant genotype for the +331G/A polymorphism was identified. The frequencies of polymorphic alleles for the +331G/A polymorphism was 30.9%. In conclusion, the +331G/A progesterone receptor gene polymorphism was present in endometriosis patients in Palembang, South Sumatra. This finding may warrant further studies to determine whether this polymorphism play a role in the development of endometriosis in the Indonesian population.

Results of combined treatment of uterine leiomyoma in women of reproductive age

The purpose of the work. To study the effectiveness of the combined treatment of uterine leiomyoma (UL), taking into account the possibility of realizing reproductive function.Material and methods. The total number of women of reproductive age examined with a large UL (a dominant node more than 50 mm in diameter) was 94. At the first stage, all patients received preoperative preparation. At the first stage all patients received preoperative preparation. 35 patients with concomitant endometrial hyperplasia and/or with the presence of the progesterone receptor gene polymorphism PGR progins received aGn-RH in an average therapeutic dose once in 28 days, 3 injections. 59 patients with the reference genotype without endometrial pathology received mifepristone 50 mg daily for 3 months. After preoperative preparation, the patients underwent conservative myomectomy by laparotomy. Menstrual function, pelvic pain syndrome, size of leiomatous nodules, drug tolerance, frequency of pregnancy and recurrence were assessed. Statistical data processing was performed using Microsoft Excel software. The main statistical indicators such as frequency, mean and standard deviation were taken into account. The results were considered significant at p < 0.05.Results. Excessive menstruation and AUB occurred in 81.9% of patients. Amenorrhea occurred in 79.8% of patients after 1 month of therapy and in all patients after 3 months. Recovery of menstruation was noted in 10.6% of patients a month after the operation, in 59.6% of patients after two months and on the third cycle menstruation resumed in all patients. The frequency of pain syndrome unrelated to the menstrual cycle decreased from 52.1% to 9.6%, dyspareunia from 12.8% to 4.3%, dysmenorrhea from 47.9% to 8.5%. According to ultrasound data, after 1 month in the group of women receiving aGn-RH the size of the nodules decreased by an average of 22.9%, and after mifepristone by 16.9%, and after 3 months by 51.4% and 45.8%. The uterine volume decreased by 28.6% and 30.5%. Starting from the second month of treatment, symptoms caused by estrogen deficiency were noted in 39.4% of patients treated with aGn-RH and 20.3% in the mifepristone group. Overall, the treatment was defined as effective in 88.6% of the women treated with aGn RH and 93.2% of those treated with mifepristone. Relapse occurred in 11.4% of women after aGn-RH and in 5.1% of those in the mifepristone group. Pregnancy occurred in 69.2% of patients and resulted in delivery in 90.8% of cases.Conclusions. The use of preoperative hormonal preparation and a differentiated approach to medication selection leads to normalization of the patient's condition and a reduction in the size of the nodules, which allows organ-preserving surgical treatment with minimal uterine trauma. Preference should be given to anti-gestagens because, with equal efficiency compared to aGn-RH, they are better tolerated by patients and have a more pronounced positive effect on process stabilization and disease recurrence. This combined approach improves treatment efficiency to 91.5%, preserves the uterus in reproductive-age women and promotes pregnancy in 69.2% of cases.

Exploring the Genetic Background of the Differences in Nest-Building Behavior in European Rabbit.

Simple SummaryThe rabbit is one of the genetically most diverse farm animals, where domestication has resulted in a change primarily in the genes responsible for behavior. The elements of intensive production technology (e.g., nursing, change of nest material) can have a significant effect on maternal behavior. Its individual variability is evident in the timing of nest building and nest composition. As a result that the hormone progesterone strongly influences the steps of nest building, we investigated the association of genetic mutations in the progesterone receptor gene with nest-building behavior in wild-type rabbit does. In addition to the already described point mutations in domesticated lines, we detected a new mutation in our wild type rabbits. However, the timing of nest building (hay carrying) was related to an already described point mutation. The heritability of this trait was low, but it confirms the genetic determination of the behavior besides the environmental factors. One of the genotypes was responsible for the two days earlier initiation of the hay carrying behavior. The early initiation of this process allows animals to construct a high-quality nest resulting in better survival of the offsprings in nature.Once a day, nursing and absentee mothering make the wild rabbit (Oryctolagus cuniculus) an ideal model animal for measuring differences in maternal behavior. Behavioral events and their hormonal regulation leading to parturition are well documented; however, the genetic background behind individual differences in this complex process is unknown. Decreased progesterone hormone level and the reduction of progesterone receptor activity are crucial to initiating the collection of nest material. The progesterone receptor gene is a likely candidate affecting nest-building behavior. In addition to several known point mutations in the progesterone receptor gene of the European wild rabbit, we have found a new mutation in the promoter region of the gene at 2682 T > C. Although this new single nucleotide polymorphism (SNP) was not involved in the formation of the nest-building behavior, an SNP (2464G > A) already described in the promoter region showed an association with individual differences in the initiation of hay carrying. The distribution of this SNP delivered an opposite result compared to domestic rabbits. Genotype (GG) with high uterine capacity was most frequent; the hereditary value of the trait was h2 = 0.10. Thus, progesterone receptor gene polymorphism may manifest in individual differences affecting breeding success in this species.

Вовлеченность полиморфизма генов рецепторов эстрогенов и прогестерона в развитие миомы матки

Вовлеченность полиморфизма генов рецепторов эстрогенов и прогестерона в развитие миомы матки

Analysis of estrogen and progesterone receptor gene polymorphisms in leiomyoma.

Leiomyoma, one of the most common benign tumors, causes morbidity during the reproductive years in women. The molecular pathogenesis of the disease is not clear. Leiomyomas are hormone-sensitive tumors affecting around 20%-25% of women. Gene polymorphism studies could be important and explaining in the evaluation of multifactorial diseases such as leiomyoma. Polymorphisms involving genes responsible for the synthesis and signalization of steroid hormones could be used as genetic markers for hormone-related conditions. The purpose of this study was to analyze the effect of ERα-351 XbaI A/G, ERα-397 PvuII T/C, and progesterone receptor (PGR) PROGINS polymorphisms on the development of leiomyomas. In this study, 213 samples (103 leiomyoma patients and 110 healthy controls) participated. The ERα-351 XbaI A/G and ERα-397 PvuII T/C gene polymorphisms were analyzed using PCR-RFLP method. PGR PROGINS polymorphism was analyzed by PCR method with specific primers. The genotype distribution and allele frequency of the ERα-351 XbaI A/G, ERα-397 PvuII T/C, and PGR PROGINS polymorphisms were not statistically different between leiomyoma patient and control groups (p>0.05). This study reflects that ERα and PGR PROGINS polymorphisms may not be one of the many genetic factors for leiomyoma susceptibility.

The Alu-insertion progesterone receptor gene polymorphism is not associated with breast cancer: a meta-analysis

BackgroundThe role of progesterone receptor (PGR) gene polymorphisms in breast cancer is still controversial. Here, we performed a meta-analysis to determine whether the Alu insertion is associated with an increased risk of breast cancer and, further, whether the Alu insertion contributes to the development of breast cancer.MethodsUsing database searches, we selected 10 controlled case studies that met a rigorous set of inclusion criteria; these studies included 2106 cases and 1660 controls. We generated odds ratios and 95% confidence intervals in order to determine the strength of the relationship between the Alu insertion and breast cancer incidence. We also performed additional subgroup analyses and sensitivity analyses to further clarify the relationship.ResultsUsing a random effects model, we concluded that the Alu insertion was not associated with the risk of breast cancer under the dominant genetic model; the pooled OR was 1.025 (95% CI = 0.526–1.994, p = 0.943). When a subgroup analysis was performed according to ethnicity, we found that the Alu insertion was associated with breast cancer incidence in Indians and Indo-European mixed racial groups, but the association disappeared for patients of Caucasian or Latino decent.ConclusionsOur meta-analysis showed that the Alu-insertion progesterone receptor gene polymorphism was not associated with breast cancer. These results provide further information regarding the association between the Alu insertion in the PGR gene and the incidence of breast cancer.

Progesterone Receptor (PGR) Gene Variants Associated with Breast Cancer and Associated Features: a Case-Control Study.

Insofar as altered estrogen receptor-progesterone receptor (PR) expression contribute to breast cancer pathogenesis, previous studies examined the association of genetic variation in PR gene (PGR) with breast cancer, but with mixed outcome. We evaluated the association between PGR variants, and breast cancer and associated features. A retrospective case-control study involving 183 female breast cancer patients, and 222 control women. PGR genotyping was done by real-time PCR. Minor allele frequencies of rs1042838, rs590688, and rs10895068 PGR gene polymorphisms were significantly higher in breast cancer patients compared to controls. Patients carrying rs1042838 G/T, rs590688 C/C, and rs10895068 G/A genotypes had higher risk of breast cancer, while carriage of rs3740753 G/G genotype was associated with marginal reduction in breast cancer risk. In addition, carriage of rs1042839, rs3740753, and rs10895068 minor allele was associated with Her2 status, while rs3740753 and rs10895068 were associated with effective hormone replacement therapy. Furthermore, carriage of rs10895068 minor allele in breast cancer women were also associated with age at first pregnancy, hormone receptor (RH) status, and previous use of oral contraceptives. PGR haploview analysis documented moderate-strong linkage disequilibrium (non-random association of alleles at different loci) between 7 of the 8 tested PGR SNPs, thus allowing construction of 7-locus PGR haplotypes. Two haplotypes, ATGCCGA and GTGCCGA, both containing rs590688, were positively associated with breast cancer, thus assigning a breast cancer-susceptible nature to these haplotypes. PGR rs1042838, rs590688, and rs10895068, and ATGCCGA and GTGCCGA haplotypes are related with increased breast cancer susceptibility in Tunisian women.

RISK FACTORS STUDY OF THREATENED ABORTION OCCURRING IN WOMEN WITH REGARD TO PROGESTERONE RECEPTOR GENE POLYMORPHISM

Relevance. An important medical and social problem of modern obstetrics is threatening abortion. Among all threatened abortion risk factors today a special attention is given to genetic factors, in particular, to progesterone receptor gene polymorphism. From a progesterone receptor gene polymorphism may depend a progesterone receptor response and a threatened abortion occurring. Determination of the relationship between a progesterone receptor gene polymorphism and miscarriage should be in a priority of modern obstetrics. Objective: to evaluate risk factors in threatening abortion occurring and a significance of progesterone receptor gene polymorphism among them. Materials and methods. The study included 197 women at the gestational age of 8-16 weeks., which were divided into 2 groups The first study group consisted of 102 practically healthy pregnant women. The second study group included 95 patients diagnosed with a threatened abortion. The following research methods were used: clinical, questionnaires, laboratory, instrumental, genetic, statistical. In addition to clinical, laboratory, instrumental and statistical research methods, a questionnaire was conducted to determine a stress level and special molecular genetic studies were performed to determine gene polymorphism. Results. The homozygous carriage of the G-allele by the progesterone receptor gene polymorphism (SNP PGR) rs590688 (p=0,028) and the high stress level by Perceived Stress Scale (p=0,007) are factors that are associated with a high risk of threatened abortion occurring in women. In homozygous G-allele carriers by SNP PGR rs590688 the risk of a threatened abortion occurring is 2.5 times higher than in carriers of other genotypes by this polymorphism (p=0,02). Conclusion. The most significant risk factors for threatened abortion occurring in women are progesterone receptor gene polymorphism rs590688 and the stress level by the Perceived Stress Scale. The analysis of SNP PGR and a stress level should be used in threatening abortion risk factors evaluation.

No association between the progesterone receptor gene polymorphism (+331G/a) and the risk of breast cancer: an updated meta-analysis

BackgroundMany published studies have estimated the association between the +331G/A (rs10895068) polymorphism in the progesterone receptor (PgR) gene and breast cancer risk. However, the results remain inconsistent and controversial. To address this inconsistency, we systematically interrogated the aforementioned association via a meta-analysis.MethodsThrough a literature search, we identified 13 case-control studies, including 12,453 cases and 14,056 case-free controls. The strengths of reported associations were evaluated using odds ratios (ORs) with 95% confidence intervals (95%CIs).ResultsAn association was found between +331G/A polymorphism and +331G/A risk in the dominant model (p = 0.027). Via subgroup analysis, we found no association between +331G/A and breast cancer risk in Caucasians, Asians or mixed racial groups.ConclusionsThrough meta-analysis, we were able to gain insight into previously reported associations between +331G/A polymorphism and breast cancer risk. However, further studies are still needed to provide more evidence.

Association of Progesterone Receptor Gene Polymorphisms in Promoter Region with Ovarian Endometriosis in Indonesian Women

Association of Progesterone Receptor Gene Polymorphisms in Promoter Region with Ovarian Endometriosis in Indonesian Women

Progesterone Receptor Gene Polymorphisms of rs1042838 and New Mutation in Ovarian Endometriosis in Indonesian Women

Progesterone Receptor Gene Polymorphisms of rs1042838 and New Mutation in Ovarian Endometriosis in Indonesian Women

Progesterone resistance in endometriosis: origins, consequences and interventions.

Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone-resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered microRNA expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral GnRH antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment.

Progesterone receptor (PRG) gene polymorphism and association with litter size in the california rabbit breed

Modern approaches to genetic improvement of species based on genotype-depth evaluation of farm animals and genetic diversity of populations using marker technology. Determination of genotype of animals was carried out using PCR-RFLP. A 558-bp sequence of the rabbit progesterone receptor promoter region (PGR) gene was obtained for 60 animals of the California breed from High Litter Size (HLS) and Low Litter Size (LLS) groups. Found that in individuals with multiple groups rabbit dominated by individuals with heterozygous genotype (0.700), while in animals with low levels litter size – individuals with genotype AA. In addition, the rabbit and the second group were characterized by very high actual heterozygosity (Ho = 0,700), which significantly exceeds the expected heterozygosity (No = 0.455). Among the animals that had low bahatoplidnosti differences between actual and expected assessments heterozygosity less significant (0.400 and 0.320, respectively). Thus, in both groups, there is an excess of heterozygosity, accompanied by negative assessments fixation index. PCR-RFLP for PGR gene (using the Eco31I restriction endonuclease) revealed two genotypes of AA and GA, and the genotype AA yielding a single 558 bp band, and the heterozygote genotype GA yielding all the three bands of 558, 416 and 142 bp. The 2464G > A SNP for PGR gene was not fixed in the HLS and LLS groups, the allele G frequency being 0.350 in the HLS and 0.200 in the LLS group. Whatever belong to a group marked predominance on the number of rabbits for a rabbit genotype GA on individuals who had genotype AA. More significant, the difference was for the rabbit of the I-th group (9.1 and 7.0 rabbits, respectively). The difference in litter size between the AA and GA genotypes was found for rabbits from as the HLS, as LLS group.

Threatened abortion treatment efficacy depending on progesterone receptor gene polymorphism

Threatened abortion treatment efficacy analysis was performed in 67 fertility women in gestation age 8-16 weeks depending on progesterone receptor gene polymorphism (SNP PGR) rs590688 and rs500760. SNP PGR rs590688 has a statistically significant impact on the course of threatened abortion. Positive homozygotes СС SNP PGR rs590688 associate with severe clinical current and oral natural micronized progesterone therapy worst response. SNP PGR rs500760 showed no statistically significant effect neither on the therapeutic response to clinical current nor on progesterone treatment in patients with threatened abortion.

Progesterone Receptor (PGR) gene polymorphism is associated with susceptibility to preterm birth.

BackgroundPreterm birth (PTB) is the major cause of death in newborn and the second major cause of death in children less than 5 years old worldwide. Genetic polymorphism has been implicated as a factor for the occurrence of preterm birth. The aim of this study is to evaluate whether polymorphism in the progesterone receptor (PGR) is associated with susceptibility to preterm birth.MethodsA total of 135 women with preterm and 532 women with term deliveries were genotyped for PGR gene polymorphisms (rs660149, rs471767, rs10895068) using Sequenom MassARRAY platform.ResultsThe G allele of PGR rs660149 polymorphism was significantly associated with susceptibility to PTB in the Malay women. The odds of G allele occurring among Malay women with preterm delivery was twice that of Malay women with term delivery (OR 2.3, 95 % CI (1.2–4.5, P = 0.011). Alternatively, no significant association was observed between PGR rs660149 polymorphisms and susceptibility to PTB in Chinese and Indian women.ConclusionsThis study shows that variability in the occurrence of PTB across ethnicities in Malaysia is partly due to differences in genetic background. We therefore suggest that in addition to life style and environmental factors, genetic factor should be greatly considered in this population. Prior information on the genetic composition of women may help in the identification and management of women at risk of preterm birth complication.

Progesterone receptor gene (PROGINS) polymorphism correlates with late onset of migraine.

Progesterone influences central neuronal excitability, a key event in migraine pathophysiology. Progesterone receptor gene (PGR) rs1042838 (G/T - Val660Leu) variant is indicative of PROGINS haplotype and associated to a reduced PGR activity. With the aim of investigating whether any type of association existed between this genetic variant and migraine pathophysiology, genotyping was performed in 380 consecutive migraine patients and 185 age-, sex-, and race-ethnicity-matched healthy controls from Interinstitutional Multidisciplinary BioBank (BioBIM) of IRCCS San Raffaele Pisana, Rome, Italy. rs1042838 genotypes did not correlate with demographics or clinical migraine features. However, TT (Leu) genotype was significantly associated with a later age of migraine onset: Patients affected by migraine with aura showed a linear relationship between copy number of the T allele carried by the individual and the age of migraine onset. Our data suggest that the PROGINS PGR polymorphism does not directly predispose to migraine but significantly delays migraine onset probably via a reduction in brain neuronal excitability.

Association of the +331G/A progesterone receptor gene (PgR) polymorphism with risk of endometrial cancer in Caucasian women: a meta-analysis.

The +331G/A progesterone receptor (PgR) gene polymorphism may influence risk of endometrial cancer. However, data from published studies have been controversial. To evaluate whether combined evidence shows an association between this polymorphism and endometrial cancer, we considered all available studies in a meta-analysis. We searched PubMed and EMBASE and identified eight studies representing data for 3,790 cases and 6,458 controls. We estimated risk [odds ratio (OR) and 95 % confidence interval] of these associations, which were non-significant in the entire body of results. Overall effects indicated increased risks, slightly pronounced in the homozygous and recessive models (OR 1.16-1.17, p = 0.57-0.60). These effects were exacerbated when confined to studies in Hardy-Weinberg Equilibrium (OR 1.33-1.36, p = 0.33-0.35) and in the underpowered subgroup (OR 1.62-1.68, p = 0.27-0.30). The exception is the powered subgroup which showed reduced risk (OR 0.96-0.97, p = 0.92-0.93). None of the comparisons were heterogeneous, in fact, 10 of the 16 comparisons had zero heterogeneity (I (2) = 0 %). In summary, the non-significant results suggest that the PgR +331G/A polymorphism might not be a conspicuous low-penetrant risk factor for developing endometrial cancer.

Association of the progesterone receptor gene polymorphism (PROGINS) with endometriosis: a meta-analysis.

Reported associations of progesterone receptor gene polymorphism (PROGINS) with endometriosis have been inconsistent. To evaluate the association between the PROGINS polymorphism and the risk of endometriosis. A meta-analysis of 12 published case-control studies with a total sample size of 3,321 (1,323 cases/1,998 controls) was performed. We estimated the risk (odds ratio [OR] 95 % confidence intervals) of endometriosis association with the PROGINS polymorphism. An association between the presence of the variant allele and risk of endometriosis was found, more in the homozygous and recessive models (OR 1.41-1.43, p = 0.15-0.17), and less in the dominant and co-dominant models (OR 1.22, p = 0.11-0.15). Reanalysis without the studies whose controls deviated from the Hardy-Weinberg Equilibrium did not materially alter the dominant and co-dominant effects (OR 1.19-1.22, p = 0.19-0.32), but exacerbated the homozygous and recessive effects (OR 1.59, p = 0.09). The subgroups based on geography showed increased risk associations, consistently significant in the European (OR 1.52-2.72, p = 0.0008-0.03) but not in the Brazilian studies, where ORs ranged from reduced (OR 0.70-0.74, p = 0.54-0.61) to increased (OR 1.11, p = 0.75) risks. Heterogeneity was confined in all comparisons to the dominant and co-dominant models (I (2) = 38-70 %), except in the European subgroup, which had zero heterogeneity (I (2) = 0 %) in all genetic models, as did all homozygous and recessive effects. This meta-analysis provides a comprehensive profile of the role of the PROGINS polymorphism in endometriosis by exploring the magnitude of the summary effects with modifier analysis. This magnitude is expressed with modulation or exacerbation of the summary effects, as defined by the parameters of the analysis. Thus, the results showed trend towards an increased risk of the variant PROGINS allele and susceptibility for the endometriosis.