Interleukin-8 polymorphism associated with low risk of endometriosis-related pelvic pain

INTRODUCTION AND OBJECTIVES: Endometriosis is a gynecological inflammatory disorder described as the presence of ectopic endometrial glands and stroma outside the uterus, affecting 10% of reproductive age women. Among the recurrent symptoms, the most prevalent in endometriosis are dysmenorrhea, chronic pelvic pain, dyspareunia and infertility. Although the disease’s etiology is not entirely understood, there are evidence that genetic factors and inflammatory processes may contribute to endometriosis development, also, it may be a precursor of gynecological tumors, such as ovarian cancer. Inflammation is characterized by infiltration of inflammatory cells and tissue up-regulation of cytokines such as interleukin (IL)-8. IL-8 is a chemokine known to be involved on endometriosis pathogenesis, which increase vascular permeability and production of angiogenic factors even as stimulates proliferation of endometrial cells. Some studies have shown that IL-8 was overexpressed in women with endometriosis cases compared to endometriosis free women, and thus, single nucleotide polymorphisms (SNPs) in this gene may affect its expression. The IL-8 rs4073 (-251) A>T SNP is commonly associated with up-regulation of IL-8 expression. The aim of the study was to investigate the role of IL-8 rs4073 A>T SNP in endometriosis’ development and its related symptoms. MATERIAL AND METHOD: This case-control study included 207 women with endometriosis (cases) and 193 without the disease (controls) recruited in two reference hospitals from Brazil. Genotyping of the SNP was performed by the real time polymerase chain reaction using TaqMan validated assay. Associations were evaluated by a binary logistic regression model, using odds ratios (OR) and 95% confidence intervals (CI). RESULTS AND CONCLUSION: The results showed that cases were younger (36 ± 6.8 versus 39 ± 8.4), had a lower body mass index (26.5 ± 5.3 Kg/m 2 versus 35.7 ± 6.3 Kg/m 2 ), a high frequency of all painful endometriosis-related symptoms and infertility (48.8% versus 14.0%) than the controls (P<0.001). Minor allele frequencies were 42.3% for cases and 39.9% for controls. There were no significant associations between the IL-8 rs4073 SNP and the development or staging (controls versus DIE cases, and controls versus III/IV cases) of endometriosis. However, the SNP was associated with chronic pelvic pain among endometriosis cases (AT+TT model, OR=0.54; 95% CI=0.29-0.98). Therefore, the present study hypothesized that the IL-8 rs4073 A>T SNP contributes to lower IL-8 expression and, consequently, decreases endometriosis-related pelvic pain in women with endometriosis. Finally, these data can contribute to the accurate diagnosis of the symptoms of the disease, preventing its complications, and assisting in the individualized treatment of women with endometriosis.