Photo Credit: Mohammed Haneefa Nizamudeen
The following is a summary of “Effect of Circulating Inflammatory Proteins on Endometriosis: A Mendelian Randomization Study,” published in the November 2024 issue of Obstetrics and Gynecology by Wei et al.
Endometriosis is a complex gynecological disorder described by the implantation of endometrial tissue outside the uterus, leading to pain and infertility, with immune mediators playing a pivotal role in its unclear etiology.
Researchers conducted a retrospective study using Mendelian randomization (MR) to assess the causal relationship between inflammatory proteins and endometriosis.
They filtered genetic variants associated with inflammatory proteins from a genome-wide protein quantitative trait locus study using stringent thresholds. These variants were utilized as instrumental variables (IVs) to assess the causal effects of inflammatory proteins on endometriosis. A two-sample MR analysis was conducted using endometriosis data from the UK Biobank as the outcome, with a sensitivity analysis performed to account for potential confounders. It was replicated in an independent endometriosis cohort from FinnGen, followed by a meta-analysis of MR results from both cohorts. Lastly, the causality between inflammatory proteins and endometriosis subtypes was assessed.
The results showed that the independent MR analysis revealed a negative causal association between genetically higher CXCL5 levels and endometriosis risk. This causal link remained significant in the meta-analysis. Moreover, the causal relationship of CXCL5 expression was identified in ovarian and pelvic peritoneal endometriosis.
Investigators concluded the MR analysis showed the protective role of CXCL5 against endometriosis, suggesting its potential involvement in the disease pathogenesis.
