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Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis

Abstract: OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Ann Rheum Dis. 2019 Mar;78(3). pii: e214158

Editorial: BMJ Publishing Group

 Año de publicación: 2019

Nº de páginas: 10

Tipo de publicación: Artículo de Revista

 DOI: 10.1136/annrheumdis-2018-214158

ISSN: 0003-4967,1468-2060

Url de la publicación: http://dx.doi.org/10.1136/ annrheumdis- 2018- 213588

Autores/as

ATERIDO, ADRIÀ

CAÑETE, JUAN D.

TORNERO, JESÚS

FERRÁNDIZ, CARLOS

PINTO, JOSÉ ANTONIO

GRATACÓS, JORDI

QUEIRÓ, RUBÉN

MONTILLA, CARLOS

TORRE-ALONSO, JUAN CARLOS

PÉREZ-VENEGAS, JOSÉ J.

FERNÁNDEZ NEBRO, ANTONIO

MUÑOZ-FERNÁNDEZ, SANTIAGO

GONZÁLEZ, CARLOS M.

ROIG, DANIEL

ZARCO, PEDRO

ERRA, ALBA

RODRÍGUEZ, JESÚS

CASTAÑEDA, SANTOS

RICARDO BLANCO ALONSO