DNA strands forming a joint symbolizing PsA genetic research.

Decoding Psoriatic Arthritis: New Genetic Clues & Potential Drug Targets

Kai Mendoza in Health & Wellness December 2025 • 4 min read.

"Groundbreaking research identifies a specific genetic pathway linked to psoriatic arthritis, opening doors for more effective and targeted treatments."

Psoriatic arthritis (PsA) affects nearly a third of individuals with psoriasis, impacting their quality of life. While treatments for psoriasis often extend to PsA, their effectiveness can vary. This has prompted a deeper investigation into the unique biological mechanisms driving PsA, with the goal of developing more targeted therapies.

Genetics play a significant role. Studies reveal that PsA has a higher rate of familial aggregation than psoriasis alone, suggesting specific genetic risk factors are at play. While research has identified numerous genetic markers associated with psoriasis, pinpointing the variations specific to PsA has been challenging.

Now, a new study offers a breakthrough. Researchers have identified a specific genetic pathway, glycosaminoglycan (GAG) metabolism, linked to PsA but not to psoriasis or rheumatoid arthritis. This discovery paves the way for innovative treatment strategies.

Unlocking the Genetic Puzzle: The Glycosaminoglycan (GAG) Connection

DNA strands forming a joint symbolizing PsA genetic research.

The research team conducted a genome-wide association study (GWAS) involving 835 PsA patients and 1,558 controls from Spain. They followed up with a meta-analysis using data from a North American cohort of 2,847 individuals. This comprehensive approach allowed them to pinpoint genetic variations associated with PsA at both the single marker and pathway levels.

One key finding was the identification of a new PsA risk single-nucleotide polymorphism (SNP) at the B3GNT2 locus. More significantly, the researchers discovered 14 genetic pathways significantly associated with PsA. Among these, the glycosaminoglycan (GAG) metabolism pathway stood out.

GAG metabolism is crucial for cartilage, the primary target tissue in PsA-related joint destruction.
The GAG pathway was specifically associated with PsA.
It was not associated with purely cutaneous psoriasis or rheumatoid arthritis.

To confirm the specificity, the team tested the associated variations in cohorts of patients with purely cutaneous psoriasis (PsC) and rheumatoid arthritis (RA). The GAG metabolism pathway association held strong for PsA, confirming its unique role in the disease.

New Avenues for Treatment: Targeting the GAG Pathway

With the GAG metabolism pathway identified as a key player in PsA, researchers explored potential drug targets. Network analysis revealed NCAN, VCAN, and DCN as central genes within the pathway. Interestingly, hyaluronic acid and tromethamine, drugs already approved for other conditions, target these genes.

Further investigation showed that both hyaluronic acid and tromethamine significantly modulate the GAG pathway's functionality, suggesting they could be repurposed as potential treatments for PsA. These findings highlight the power of genetics in identifying new drug targets and repurposing existing medications for autoimmune diseases.

While these findings are promising, further research is needed to validate the utility of these drug targets in treating PsA. By focusing on the specific biological mechanisms driving PsA, researchers hope to develop more effective and targeted therapies for this debilitating condition.

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This article is based on research published under:

DOI-LINK: 10.1136/annrheumdis-2018-214158, Alternate LINK

Title: Genetic Variation At The Glycosaminoglycan Metabolism Pathway Contributes To The Risk Of Psoriatic Arthritis But Not Psoriasis

Subject: General Biochemistry, Genetics and Molecular Biology

Journal: Annals of the Rheumatic Diseases

Publisher: BMJ

Authors: Adrià Aterido, Juan D Cañete, Jesús Tornero, Carlos Ferrándiz, José Antonio Pinto, Jordi Gratacós, Rubén Queiró, Carlos Montilla, Juan Carlos Torre-Alonso, José J Pérez-Venegas, Antonio Fernández Nebro, Santiago Muñoz-Fernández, Carlos M González, Daniel Roig, Pedro Zarco, Alba Erra, Jesús Rodríguez, Santos Castañeda, Esteban Rubio, Georgina Salvador, Cesar Díaz-Torné, Ricardo Blanco, Alfredo Willisch Domínguez, José Antonio Mosquera, Paloma Vela, Simon Angel Sánchez-Fernández, Héctor Corominas, Julio Ramírez, Pablo De La Cueva, Eduardo Fonseca, Emilia Fernández, Lluis Puig, Esteban Dauden, José Luís Sánchez-Carazo, José Luís López-Estebaranz, David Moreno, Francisco Vanaclocha, Enrique Herrera, Francisco Blanco, Benjamín Fernández‐Gutiérrez, Antonio González, Carolina Pérez-García, Mercedes Alperi‐López, Alejandro Olivé Marques, Víctor Martínez‐Taboada, Isidoro González-Álvaro, Raimon Sanmartí, Carlos Tomás Roura, Andrés C García-Montero, Sílvia Bonàs-Guarch, Josep Maria Mercader, David Torrents, Laia Codó, Josep Lluís Gelpí, Mireia López-Corbeto, Andrea Pluma, Maria López-Lasanta, Raül Tortosa, Nuria Palau, Devin Absher, Richard Myers, Sara Marsal, Antonio Julià

Published: 2018-12-14

Everything You Need To Know

What is Psoriatic arthritis (PsA)?

Psoriatic arthritis (PsA) is a condition that affects individuals with psoriasis, leading to joint inflammation and other systemic issues. It's distinct from psoriasis, which primarily affects the skin, and rheumatoid arthritis, another form of arthritis. This differentiation is critical because it means that treatments for psoriasis alone may not always be effective for PsA, highlighting the need for targeted therapies.

What is the significance of the glycosaminoglycan (GAG) metabolism pathway?

The glycosaminoglycan (GAG) metabolism pathway is a genetic pathway identified in the research that is significantly associated with Psoriatic arthritis (PsA) but not with psoriasis or rheumatoid arthritis. This pathway is critical for cartilage health, which is a primary target in PsA-related joint destruction. The discovery highlights a unique biological mechanism in PsA, which is a new avenue for targeted treatments.

Why is the identification of the GAG pathway important?

Identifying the GAG pathway's role in Psoriatic arthritis (PsA) is important because it provides a potential target for new therapies. By understanding the specific genetic variations and pathways involved in PsA, researchers can develop drugs that specifically address the underlying causes of the disease. This approach contrasts with treatments for psoriasis that might only partially address the joint symptoms of PsA. The discovery opens doors to more effective and targeted treatments, improving the quality of life for individuals with PsA.

How did the researchers identify the genetic pathway related to Psoriatic arthritis?

The research team used a genome-wide association study (GWAS) combined with a meta-analysis. This involved analyzing the genetic information of a large number of Psoriatic arthritis (PsA) patients and control groups from Spain and North America. They looked for single-nucleotide polymorphisms (SNPs) and genetic pathways associated with PsA. This comprehensive approach allowed them to pinpoint specific genetic variations and pathways related to the disease. The study's rigor is enhanced by its multi-cohort design.

What are the implications of targeting the GAG pathway for treating Psoriatic arthritis (PsA)?

The research identified NCAN, VCAN, and DCN as central genes within the glycosaminoglycan (GAG) metabolism pathway. Existing drugs like hyaluronic acid and tromethamine, which are approved for other conditions, target these genes. This suggests that these drugs, or similar ones, could be repurposed or modified to treat Psoriatic arthritis (PsA), offering a potential shortcut in drug development. The use of these types of drugs may improve the speed in which the research can be used for the patients.