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Identification of key genes and pathways associated with sex differences in rheumatoid arthritis based on bioinformatics analysis

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Abstract

Introduction

Women are more likely than men to develop the chronic, progressive autoimmune disease known as rheumatoid arthritis (RA). Although there may be a complex interplay between sex-based differences and autoimmune dysfunction. Their function in RA is largely unknown, though. The purpose of this study was to pinpoint the crucial genes and metabolic pathways that control biological variations in RA between men and women.

Methods

First, the Gene Expression Omnibus database’s gene expression information for GSE39340 and GSE55457 was downloaded (GEO). R software was used to find each of the individually identified differentially expressed genes (DEGs) between the sexes. DEGs that overlapped were found. The interactions between the overlapping DEGs were then further examined using a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology tools, respectively, were used to perform enrichment analyses.

Results

According to our findings, there were 1169 DEGs that overlapped between RA males and females, comprising 845 up-regulated genes and 324 down-regulated genes. Ten hub genes, including PIK3R1, RAC1, HRAS, PTPN11, UQCRB, NDUFV1, EGF, UBA1, UBE2G1, and UBE2E1, were discovered in the PPI network. According to a functional enrichment analysis, these genes were primarily enriched in neurodegenerative illnesses, including various disease pathways, MAPK signaling, insulin signaling, and autophagy.

Conclusion

The current data point to the possibility that the MAPK pathway and autophagy may be significant contributors to sex differences in RA. PTPN11, EGF, and UBA1 may be important genes linked to the gender development of RA and are anticipated to be therapeutic targets for the disease.

Key Points

• Our research point to the possibility that the MAPK pathway and autophagy may be significant contributors to sex differences in RA.

• PTPN11, EGF, and UBA1 may be important genes linked to the gender development of RA and are anticipated to be therapeutic targets for the disease.

• These findings may aid in the development of novel diagnostic and treatment techniques for RA in men and women.

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Funding

This work was supported by the Scientific Research Fund of Sichuan Health and Health Committee (no. 20PJ311).

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Author notes

  1. Tingting Wang and Fanxin Zeng contributed equally to this work and are regarded as co-first authors.

Authors and Affiliations

  1. Department of Rheumatology, Dazhou Central Hospital, Sichuan, Dazhou, 635000, China

    Tingting Wang, Yuanli Wei, Dongmei Wang, Weihua Zhang, Huanhuan Xie, Lingli Wei, Siying Xiong, Caizhen Liu & Jianhong Wu

  2. Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan, China, 635000

    Fanxin Zeng, Xue Li & Shilin Li

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  1. Tingting Wang
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Contributions

Tingting Wang designed the study. Fanxin Zeng and Jianhong Wu supervised the study. Tingting Wang, Fanxin Zeng, Xue Li, Yuanli Wei, Shilin Li, Dongmei Wang, and Weihua Zhang analyze the data. Tingting Wang, Huanhuan Xie, Lingli Wei, Siying Xiong, Caizhen Liu, and Xue Li did the digital visualization. Tingting Wang and Jianhong Wu wrote and revised the manuscript. All authors read and approved the final manuscript. All the authors agreed to publish the article. Tingting Wang and Fanxin Zeng contributed equally to this work and should be regarded as co-first authors.

Corresponding author

Correspondence to Jianhong Wu.

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Wang, T., Zeng, F., Li, X. et al. Identification of key genes and pathways associated with sex differences in rheumatoid arthritis based on bioinformatics analysis. Clin Rheumatol 42, 399–406 (2023). https://doi.org/10.1007/s10067-022-06387-6

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  • DOI: https://doi.org/10.1007/s10067-022-06387-6

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