Identification of Potential Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis

Front Endocrinol (Lausanne). 2021 Nov 18:12:731107. doi: 10.3389/fendo.2021.731107. eCollection 2021.


Background: Androgen insensitivity syndrome (AIS) is a rare X-linked genetic disease and one of the causes of 46,XY disorder of sexual development. The unstraightforward diagnosis of AIS and the gender assignment dilemma still make a plague for this disorder due to the overlapping clinical phenotypes.

Methods: Peripheral blood mononuclear cells (PBMCs) of partial AIS (PAIS) patients and healthy controls were separated, and RNA-seq was performed to investigate transcriptome variance. Then, tissue-specific gene expression, functional enrichment, and protein-protein interaction (PPI) network analyses were performed; and the key modules were identified. Finally, the RNA expression of differentially expressed genes (DEGs) of interest was validated by quantitative real-time PCR (qRT-PCR).

Results: In our dataset, a total of 725 DEGs were captured, with functionally enriched reproduction and immune-related pathways and Gene Ontology (GO) functions. The most highly specific systems centered on hematologic/immune and reproductive/endocrine systems. We finally filtered out CCR1, PPBP, PF4, CLU, KMT2D, GP6, and SPARC by the key gene clusters of the PPI network and manual screening of tissue-specific gene expression. These genes provide novel insight into the pathogenesis of AIS in the immune system or metabolism and bring forward possible molecular markers for clinical screening. The qRT-PCR results showed a consistent trend in the expression levels of related genes between PAIS patients and healthy controls.

Conclusion: The present study sheds light on the molecular mechanisms underlying the pathogenesis and progression of AIS, providing potential targets for diagnosis and future investigation.

Keywords: RNA transcriptome; androgen insensitivity syndrome; differentially expressed genes; immune; metabolism; reproduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Androgen-Insensitivity Syndrome / diagnosis*
  • Androgen-Insensitivity Syndrome / genetics
  • Biomarkers / metabolism*
  • Case-Control Studies
  • Child
  • Computational Biology / methods*
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology*
  • Male
  • Prognosis
  • Protein Interaction Maps
  • Transcriptome*
  • Young Adult


  • Biomarkers