Role of HLA-DRA-CREB3L4 regulatory axis in the pathogenesis of ovarian endometriosis: Inhibition of CREB3L4 expression by HLA-DRA increases the risk of disease

Weiwei Song, Sisi Jin, Jin S, Gang Wang, Wang G, Yining Zhou, Yiqiang Zhou, Zhou Y, Juan Yu, Yu J
Journal of Reproductive Immunology · 2025 · vol. 172 , pp. 104798 · doi:10.1016/j.jri.2025.104798 · PMID:41232153 · W4416239729
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This study investigated the HLA-DRA-CREB3L4 axis and found that HLA-DRA inhibits CREB3L4 expression, thereby increasing the risk of ovarian endometriosis.

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Abstract

BACKGROUND: Ovarian endometriosis is a common gynecological condition characterized by the abnormal growth of endometrial-like tissue in locations outside the uterus, and its development remains poorly understood. This study aims to investigate potential protein regulatory networks and assess their impact on disease risk using both protein quantitative trait locus (pQTL) analysis and Mendelian randomization (MR) techniques. METHODS: This study systematically integrates two major genome-wide pQTL databases, UKB-PPP and deCODE, to identify pQTL signals associated with ovarian endometriosis. Additionally, we utilized the GEO database to validate differences in protein expression. We conducted a Mendelian randomization analysis to further explore the regulatory relationships between proteins and their roles in disease development. RESULTS: After the Bonferroni correction, we identified 33 pQTL signals from UKB-PPP and 19 pQTL signals from deCODE. Among these, 8 signals from UKB-PPP and 3 signals from deCODE were validated based on expression differences. The mediation analysis results indicate that HLA-DRA significantly increases the risk of developing ovarian endometriosis by inhibiting the expression of CREB3L4 (with a mediation proportion of 13.99 %), and the direction of the mediation effect is consistent with the total effect. CONCLUSION: This study provides new insights that HLA-DRA downregulates the expression of CREB3L4, which may affect the risk of developing endometriosis. The results provide new evidence for understanding the genetic and molecular basis of ovarian endometriosis and establish a theoretical foundation for the development of future diagnostic markers and targeted treatment strategies.

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Condition tags

endometriosis

MeSH descriptors

Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein Cyclic AMP Response Element-Binding Protein

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (33)

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License: CC0 · commercial use OK