Pharmacogenetic criteria for the efficacy of basic anti-inflammatory therapy for rheumatoid arthritis

• Published in: Terapevtic̆eskii arhiv Vol. 82; no. 12; pp. 56 - 61
• Main Authors: Konenkov, V I, Zonova, E V, Korolev, M A, Leonova, Iu B, Shevchenko, A V, Golovanova, O V, Prokof'ev, V F
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) "Consilium Medicum" Publishing house 01.01.2010
• Subjects: Anti-Inflammatory Agents - pharmacokinetics; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; basic anti-inflammatory therapy; DNA - analysis; Female; Follow-Up Studies; Humans; interleukin-1; Interleukins - biosynthesis; Interleukins - genetics; Male; Middle Aged; pharmacogenetics; Polymerase Chain Reaction; Polymorphism, Genetic; Prognosis; rheumatoid arthritis; tumor necrosis factor
• ISSN: 0040-3660; 2309-5342

To analyze the prognostic value of detection of allelic variants of the promoter regions of cytokine genes in patients with rheumatoid arthritis (RA) with varying efficiency of basic anti-inflammatory therapy (BAIT). Eighty-nine patients with a valid diagnosis of RA, of them there were 79 females and 10 males (mean age 52.5 +/- 13.1 years), were examined. The patients received BAIT with methotrexate in a dose of 10.0-17.5 mg/week (77.5%) or with sulfasalazine in a dose of 2.0 g/day (22.5%) for 24 weeks. The efficiency of BAIT was evaluated using the European League Against Rheumatism (EULAR) criteria (DAS28) following 24 weeks. A high therapeutic effect was stated when DAS28 decreased by more than 1.2 scores. Changes in DAS28 by less than 0.6 scores were regarded as ineffective BAIT. Cytokine gene polymorphisms were studied by restriction analysis of amplification products. The following polymorphic sites in the interleukin genes: FNOA at positions C-863A, G-308A, G-238A, IL-1BT-31C, IL-4 C-590T, IL-6 G-174C, and IL-10 C-592A, were explored. The IL-6 G-174G genotype associated with the high production of this proinflammatory cytokine and the IL-IB C-31C genotype associated with the low production of interleukin-1beta (IL-1beta) were most frequently encountered in a group of patients with the high efficiency of BAIT (22 and 24.7%). At the same time the C allele associated with the low production of IL-6 and the IL1B T-31C genotype associated with the high production of this cytokine were most frequently detected at position of G-174C of the promoter regions in the IL-6 gene in patients unresponsive to BAIT (32 and 36%). The allelic variants of the promoter regions of the IL-6 G-174G, IL-1B C-31C, IL-4 C-590T, and IL-10 C-592A can be genetically prognostic factors of formation of the high efficiency of BAIT.