INFLUENCE OF POLYMORPHISM IN THE GENES ENCODING LEPTIN AND ITS RECEPTOR IN THE DEVELOPMENT OF ENDOMETRIOSIS IN BRAZILIAN WOMEN

INTRODUCTION AND OBJECTIVES: Endometriosis is a benign and heterogeneous
gynecological disease, influenced by genetic and environmental factors. It is a pathology that negatively impacts the physical, mental, and social well-being of women due to the high presence of painful symptoms and infertility, in addition to being a risk factor for the development of gynecological cancers. In addition, the definitive diagnosis is invasive, and the pharmacological treatment is used only to alleviate the symptoms, being considered a relevant public health problem. lthough its etiopathogenesis is not fully elucidated, it is known that the endocrine pathway may play an important role in the development of endometriosis, with emphasis on the leptin hormone together with its receptor LEPR which has already been recognized as an important mediator of immune regulation, angiogenesis,
and inflammation. Single nucleotide polymorphisms (SNPs) involved in the regulation and biosynthesis of leptin (LEP) and its receptor (LEPR) are of great importance as possible genetic markers of the disease. Therefore, this study aims to evaluate the influence of LEP –2548G>A and LEPR 109A>G SNPs on the evelopment of endometriosis and its clinical characteristics in Brazilian women. MATERIAL AND METHODS: This study consisted of 237 endometriosis cases and 226 controls recruited from two referral hospitals in Rio de Janeiro. Genotyping of LEP –2548G>A and LEPR 109A>G SNPs was performed by the real-time polymerase chain reaction (PCR) technique. A binary logistic regression was used to evaluate the associations between the studied SNPs and endometriosis and its characteristics, obtaining odds ratios (OR) and their respective 95% Confidence intervals (95% CI). RESULTS AND CONCLUSION: Mean age (39 ± 8 versus 36 ± 7, espectively) and mean body mass index (28.8 ± 6.1 Kg/m2 versus 26.5 ± 5.3 Kg/m2, respectively) were significantly different between controls and cases. Endometriosis cases had a higher prevalence of all clinical symptoms of the disease, and a higher frequency of family history of endometriosis when compared to the control group (P<0.001).The variant allele frequency for LEP -2548G>A SNP was 32.7% and 28.5% for the cases and controls, respectively, and for LEPR 109A>G SNP was 17.9% and 17.9% for the cases and controls, respectively. No significant differences were found for both studied SNPs between cases and controls. However, this study observed that the LEPR 109A>G SNP was positively associated with chronic pelvic pain (OR = 1.75; 95% CI = 1.05-2.89) and dyspareunia (OR = 1.78; 95% IC = 1.01-3.12) among women with endometriosis. In conclusion, the LEPR 109A>G SNP presented an increased risk of developing chronic pelvic pain and dyspareunia in endometriosis, which may contribute to the understanding of the molecular mechanisms of the disease and to aid in the early diagnosisand exploration of therapeutic options for the painful symptoms present in women with endometriosis.