GREB1 rs13394619 POLYMORPHISM IN ENDOMETRIOSIS PROGRESSION: REPLICATION AND VALIDATION IN BRAZILIAN WOMEN

INTRODUCTION AND OBJECTIVE: Endometriosis is an estrogen-dependent multifactorial gynecological disease, which affects 10% of the female population of reproductive age. In addition to having disabling symptoms, with a high prevalence of infertility, it is also a risk factor for the development of gynecological cancers. Genetic variants have been identified in genome-wide association (GWA) studies in the endometriosis, with emphasis on the rs13394619 A>G single nucleotide polymorphism (SNP) of the growth regulating estrogen receptor binding 1 (GREB1) gene, that is involved in regulating cell growth in response to estrogen. That said, the present study was conducted to replication and validate the role of the GREB1 rs13394619 A>G SNP in the development and progression of endometriosis and its disabling symptoms in Brazilian population. MATERIAL AND METHOD: A case-control study was carried out, consisting of 237 cases with endometriosis and 237 controls, recruited from two reference hospitals in Rio de Janeiro. The real-time polymerase chain reaction (PCR) technique was used to perform genotyping of the studied SNP. The binary logistic regression model was used to evaluate the associations of endometriosis and its classifications and symptoms, and the SNP, obtaining odds ratios (OR) with 95% confidence intervals (95%CI). RESULTS AND CONCLUSION: Most cases included in the present study had advanced staging (59%) and deep infiltrative endometriosis (DIE 66%). The mean age of the case group (36±7) was lower than that of the controls (40±10; P<0.01), with most cases being in the 18-39 age range (68%) and controls over 40 years (59%). Body mass index (BMI) was different between the groups (26±5 cases and 29±6 controls; P<0.01), with 70% of cases having a normal to overweight BMI, while 64% of controls had a BMI ranging from overweight to obese. All symptoms related to endometriosis (dysmenorrhea, pelvic pain, dyspareunia, bowel and urinary symptoms, and infertility) were more frequent in cases than in controls (P<0.01). Regarding polymorphism, the frequency of the GREB1 rs13394619 AG and AA genotypes, respectively, was 36% and 12% in the group of women with endometriosis and 45% and 11% in the control group. The rs13394619 SNP showed a significant association with endometriosis, both considering all cases (GREB1 AG - OR=1.50 and IC95%=1.02-2.21), and only cases with DIE (GREB1 AG - OR=1.60 and IC95%=1.03-2.46; GREB1 AG+GG - OR=1.55 and IC95%=1.03-2.33). There was no significant association between the studied SNP and symptoms related to endometriosis. In summary, the GREB1 rs13394619 A>G SNP presented an increased risk for the development and progression of endometriosis. This polymorphism, involved in the regulation of cell growth by estrogen, may be a new biological candidate for disease progression, contributing to more effective diagnosis and targeted treatment.