The association between genetically predicted systemic inflammatory regulators and endometriosis: A bidirectional...

Area of Science:

• Genetics
• Immunology
• Reproductive Medicine

Background:

• Elevated inflammatory markers are observed in endometriosis (EMs) patients.
• A definitive causal link between these markers and EMs onset remains unestablished.

Purpose of the Study:

• To investigate the causal relationship between cellular inflammatory markers and endometriosis risk.
• To explore potential therapeutic targets for EMs based on inflammatory pathways.

Main Methods:

• Utilized a bidirectional Mendelian randomization (MR) approach.
• Employed genome-wide association study (GWAS) data for EMs and genetic associations for 41 inflammatory regulators.
• Performed inverse-variance weighted analysis with MR-Egger, weighted median, and MR-PRESSO sensitivity analyses.

Main Results:

• No significant causal association was found between most of the 41 systemic inflammatory regulators and EMs risk.
• Genetically predicted elevated Interleukin-6 (IL-6) levels were associated with an increased risk of EMs (OR=1.351).
• Genetically predicted elevated Platelet-Derived Growth Factor-BB (PDGF-BB) levels were associated with a reduced risk of EMs (OR=0.856).

Conclusions:

• Genetically elevated IL-6 may contribute to EMs development.
• Elevated PDGF-BB levels appear to have a protective effect against EMs.
• Findings suggest IL-6 and PDGF-BB as potential therapeutic targets for EMs, while other markers may be downstream effects.