BACKGROUND: Secreted Phosphoprotein 1 (SPP1) is known to play an important role in inflammation and immunity. The differences in the presentation of systemic lupus erythematosus according to sex have been widely discussed such as the more severe and rapid course of the disease in men. We analyze gene expression in tissue-specific and variant-disease association of rs9138 and rs1126616 of SPP1 gene, we got the intersection proteins that are acting in both the protein-protein pathways of testicular disease and systemic lupus erythematosus. A tissue-specific gene expression analysis was performed in the Genotype-Tissue Expression (GTEx v8), ENSEMBL and EBI-EMBL databases; focusing on tissues that could be related to inflammation processes or cells involved in the production of INF. A variant-disease association was made in DisGenet platform. Protein-protein interaction network related to testicular disease and systemic lupus erythematosus was performed in Cytoscape.
RESULTS: Tissue-specific gene expression showed a main influence on the expression in testis tissue. In the variant-disease association, rs1126616 was associated with systemic lupus erythematosus and rs9138 with autoimmune disease.17 proteins were found involved in the development of testicular disease and systemic lupus erythematosus. The pathways in which are intervening are positive regulation of cytokine production, regulation of interferon-gamma production, negative regulation of interferon-gamma production, positive regulation of interferon-gamma production, regulation of immune system process.
CONCLUSIONS: The positive association between testicular function and the development of systemic lupus erythematosus has been seen previously, particularly when there is testicular hypofunction. The key role of the rs9138 variant in activating high levels of Interferon-α and secreted phosphoprotein 1 has been reported, but the role of the rs1126616 variant has not been proposed before. It suggests that men with systemic lupus erythematosus have a higher risk of comorbidity, this may justify its consideration in the treatment of patients, this information opens avenues for future research focused on different tissues.