7729 Autoimmune Thyroid Disease And Risk of Premature Ovarian Failure - A Comprehensive Analysis Combining Observational Studies, Two-sample Mendelian Randomization Study, And Targeted Drug Forecast
Authors: Wang R , Dou T , Guan L , Qi X , Wang X , Yu C , Guan Q 
Published: October 2024

Disclosure: R. Wang: None. T. Dou: None. L. Guan: None. X. Qi: None. X. Wang: None. C. Yu: None. Q. Guan: None.

Premature ovarian failure (POF), a condition impacting women's fertility and physical well-being. Specifically, autoimmune thyroid disease (TAI) is recognized as an organ-specific autoimmune condition that may co-occur with POF in clinical scenarios, yet the precise nature of their relationship remains uncertain. The objective of this study is to investigate the influence of TAI on ovarian function, identify shared pathogenic genes, predict potentially effective drugs, and establish a foundation for clinical interventions. Firstly, a case-controlled study was conducted using the Nationwide Readmissions Database (NRD) in the United States. This involved identifying patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) as the study group, and those without deficiency as the control group, to explore the correlation with POF. Additionally, an Asian population-based case group comprising 897 patients with POF and a control group of 897 healthy women were gathered to analyze the association of POF with TAI-related antibodies, namely TGAb and TPOAb. Furthermore, a two-sample Mendelian randomization(MR) study was undertaken in European populations to investigate the causal relationship between TAI and POF. Lastly, genes associated with HT, GD, and POF were compiled from the GEO, GeneCards, and DisGeNET databases, and common genes were identified through intersection. Subsequent gene ontology and pathway enrichment analyses, protein-protein interaction analyses, and candidate drug predictions were performed based on the shared genes. The findings revealed a significant association between TAI and POF in the NRD, with patients exhibiting TAI being notably more prone to POF compared to the control group (OR 1.78, 1.34-2.35, P&lt;0.001). Subgroup analysis further demonstrated an increased risk of POF in patients with HT (OR 1.51, 1.02-2.22, P&lt;0.05) and GD (OR 2.18, 1.45-3.29, P&lt;0.05). In the Asian population, a retrospective analysis indicated a positive correlation between TPOAB positivity and POF (OR 1.76, 1.24-2.51, P&lt;0.05). MR analysis unveiled a causal relationship between GD and POF. Through a comprehensive examination of multiple gene databases, 47 common genes were identified between HT and POF, and 20 common genes between GD and POF. Enrichment analysis demonstrated relative similarities in cytokines and signal transduction, apoptosis, inflammatory response, and other aspects between HT and POF. GD was found to potentially influence ovarian function through pathways such as the PI3K-Akt signaling pathway and adhesive plaques. Dexamethasone, rapamycin, and other drugs emerged as potential therapeutic options for both diseases. In summary, our study suggests that TAI, particularly GD, may elevate the risk of POF. Additionally, we predict potential therapeutic drugs, and shed light on the potential biological mechanisms linking HT/GD and POF.

Presentation: 6/3/2024