Genetic Predispositions of Glucocorticoid Resistance and Therapeutic Outcomes in Polymyalgia Rheumatica and Giant Cell Arteritis

• Main Authors: Tomas Smutny, Ivan Barvik, Tomas Veleta, Petr Pavek, Tomas Soukup
• Format: Article
• Language: English
• Published: MDPI AG 2019-04-01
• Series: Journal of Clinical Medicine
• Subjects: pharmacogenetics; glucocorticoid resistance; giant cell arteritis; polymyalgia rheumatica
• Online Access: https://www.mdpi.com/2077-0383/8/5/582

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related chronic inflammatory diseases. Glucocorticoids (GCs) are first-choice drugs for PMR and GCA, although some patients show poor responsiveness to the initial GC regimen or experience flares after GC tapering. To date, no valid biomarkers have been found to predict which patients are at most risk for developing GC resistance. In this review, we summarize PMR- and GCA-related gene polymorphisms and we associate these gene variants with GC resistance and therapeutic outcomes. A limited number of GC resistance associated-polymorphisms have been published so far, mostly related to <i>HLA-DRB1*04</i> allele. Other genes such <i>ICAM-1</i>, <i>TLR4</i> and <i>9</i>, <i>VEGF</i>, and <i>INFG</i> may play a role, although discrepancies are often found among different populations. We conclude that more studies are required to identify reliable biomarkers of GC resistance. Such biomarkers could help distinguish non-responders from responders to GC treatment, with concomitant consequences for therapeutic strategy.