Unveiling the genetic link and pathogenesis between psoriasis and IgA nephropathy based on Mendelian randomization...

Area of Science:

• Immunology and Nephrology
• Genetic Epidemiology

Background:

• Psoriasis is frequently associated with secondary IgA nephropathy (IgAN), but underlying mechanisms remain unclear.
• Further research is needed to elucidate the connection between these two conditions.

Purpose of the Study:

• To explore the causal relationship between IgA nephropathy and various forms of psoriasis using Mendelian randomization.
• To identify potential shared genetic and molecular pathways between psoriasis and IgAN.

Main Methods:

• Mendelian randomization (MR) analysis to assess causality.
• Transcriptomic analysis of Gene Expression Omnibus databases.
• Differentially expressed gene (DEG) and weighted gene co-expression network analysis (WGCNA).
• Protein-protein interaction (PPI) network construction and analysis.

Main Results:

• MR analysis indicated that psoriasis vulgaris (OR=1.040) and arthropathic psoriasis (OR=1.081) are associated with an increased risk of IgAN in Europeans.
• Twelve potential crosstalk genes, including CXCL9, IL1β, CCL4, and MMP1, were identified.
• These genes are primarily involved in immune and inflammatory responses, with CXCL9, IL1β, CCL4, and MMP1 showing significant diagnostic value.

Conclusions:

• Genetic predisposition to IgAN may increase the risk of developing psoriasis vulgaris and arthropathic psoriasis.
• Clinicians should consider the risk of IgAN in psoriasis patients, particularly those with psoriasis vulgaris and arthropathic psoriasis, presenting with renal dysfunction.
• Chronic inflammation, drug effects, and immune system dysregulation may link the pathogenesis of psoriasis and IgAN.