Details

Autor(en) / Beteiligte

• Cuppen, Bart V. J.
• Pardali, Katerina
• Kraan, Maarten C.
• Marijnissen, Anne C. A.
• Yrlid, Linda
• Olsson, Marita
• Bijlsma, Johannes W. J.
• Lafeber, Floris P. J. G.
• Fritsch-Stork, Ruth D. E.

Titel

Polymorphisms in the multidrug-resistance 1 gene related to glucocorticoid response in rheumatoid arthritis treatment

Ist Teil von

• Rheumatology international, 2017-04, Vol.37 (4), p.531-536

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• A substantial proportion of rheumatoid arthritis (RA)-patients experience an insufficient response to glucocorticoids, an important therapeutic agent in RA. The multidrug-resistance 1 (MDR1) gene product P-glycoprotein (P-gp) is an efflux pump that actively transports substrates, such as glucocorticoids, out of the cell. We investigated if the variation in response might be explained by single-nucleotide polymorphisms (SNPs) in the MDR1 gene. RA-patients treated with intravenous methylprednisolone pulses ( n  = 18) or oral prednisone/prednisolone ( n  = 22) were included in a prospective cohort, and clinical response was measured after 5 and 30 days, respectively. The C1236T, G2677A/T, and C3435T SNPs were determined, and the functionality of P-gp was assessed by flow cytometry (Rhodamine efflux assay). Carriage of the G2677A/T SNP was significantly associated with response (OR = 6.18, p  = 0.035), the other SNPs showed trends. Stratified for received treatment, the effect was only present in methylprednisolone treated patients. Mutant allele carriage significantly decreased functionality of P-gp in B cells, though had a smaller impact in other PBMC subtypes. Carriage of a MDR1 SNP was related to a response to methylprednisolone in this study, which his suggests that RA-patients carrying wild-type alleles might benefit from P-gp inhibition or administration of glucocorticoid analogues that are non-P-gp substrates.