Influência de polimorfismos em genes envolvidos com a suscetibilidade da endometriose: via dos hormônios sexuais femininos

Endometriosis is a chronic disease, influenced by environmental, hormonal and genetic factors. As it is estrogen dependent, single nucleotide polymorphisms (SNPs) in genes involved in this pathway could promote functional changes in its proteins, influencing the development of endometriosis. Thus, the objective of this thesis was to investigate the influence of the progesterone receptor (PGR) + 331C>T, cytochrome P450 (CYP) 17A1 - 34A>G, CYP19A1 1531G>A, CYP2C19*2 and *17, and matrix metalloproteinase (MMP)-3 276A>G in the susceptibility to endometriosis, as well as to evaluate the epidemiological profile of women with this disease. To achieve the proposed objectives, five articles were elaborated. The 1st article was a descriptive study of the epidemiological characteristics of women with endometriosis recruited from 2011 to 2018. The 2nd, 3rd and 4th articles were case-control and evaluated the magnitude of association of the selected SNPs with the development of endometriosis, using logistic regression for the analyzes. Finally, a systematic review of genome-wide association (GWA) studies in endometriosis was performed. Dysmenorrhea (OR = 2.22 and 95% CI = 1.18-4.42) and pelvic pain (OR = 1.79 and 95% CI = 1.07-3.01) were associated with the irregular menstrual cycle . Dyspareunia was associated with a BMI >25kg/m2 (OR = 1.97 and 95% CI = 1.10-3.53), alcohol consumption (OR = 2.13; 95% CI 1.20-3.82 ) and superficial endometriosis (OR = 0.25 and 95% CI = 0.11-0.57). Deep infiltrative endometriosis (DIE) and stage III-IV were associated with intestinal changes (OR = 2.58; 95% CI = 1.08\20136.11 and OR = 2.75; 95% CI = 1.31-5 , 76). Women aged 30-39 years were more likely to be infertile than those aged T, CYP17A1-34A>G and CYP19A1 1531G>A were positively associated with endometriosis (OR = 1.72 and 95% CI = 1.09-2.72). SNP CYP2C19*2 was positively associated with endometriosis (OR = 1.83 and 95% CI = 1.17-2.85) and disease-related obesity (OR = 3.27 and 95% CI = 1.55 -6.89). The SNP MMP-3 276G>A was associated with cases of DIE (OR = 1.87 and 95% CI = 1.01-3.45) and infertility (OR = 3.30 and 95% CI = 1 , 31-8.33). The systematic review identified the WNT4 rs7521902, GREB1 rs13394619, FN1 rs1250248, IL1A rs6542095 and VEZT rs10859871 variants significantly associated with the susceptibility to endometriosis. The data from the present thesis may contribute to a better understanding of the disease's etiopathogenesis, in the optimization of the diagnosis and guide the clinical treatment of endometriosis.