The impact of genetic factors on response to glucocorticoids therapy in IBD

ABSTRACT

Glucocorticosteroids (GCs) are used for many years as first-line drugs for the achievement of remission in exacerbations of inflammatory bowel disease (IBD). However, close to 20% of patients are resistant to GCs, and 40% of patients become dependent on GCs. The challenge of today’s personalized medicine is the anticipation of the steroid therapy effects even before the initiation of treatment. As several studies show, individually variable response to GCs in population has a genetic background and may depend on gene variability encoding proteins involved in the function and metabolism of GCs. To those genes belong: NR3C1 – responsible for the synthesis of GC receptor (GR); Hsp90, HSP70, STIP1, FKB5 – genes of GR protein complex; ABCB1 and IPO13 coding glycoprotein p170; and importin 13 – involved in GCs transport; IL1A, IL1B, IL2, IL4, IL8, IL10, TNF, and MIF – genes of the epithelial pro-inflammatory factors synthesis, which excessive activation causes steroid resistance as well as CYP3A4 and CYP3A5 – encoding GCs biotransformation enzymes. This work systematizes and sums up the state of current knowledge in the field of pharmacogenetics as well as expectations for the future in the realm of individualized medicine in IBD patients treated with GC drugs.

KEYWORDS:

• Genes
• glucocorticosteroids
• IBD
• pharmacogenetics
• polymorphism

Acknowledgements

Marcin Gabryel is recipient of a fellowship for young researcher from Poznan Medical University (Poland) and from the Polish National Science Centre (grant no. 2015/17/N/N25/00689).

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.