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Vol 45(2011) N 6 p. 886-893; E.Y. Tsareva1,2, O.G. Kulakova1,2, O.Y. Makarycheva1, A.N. Boiko5,2, S.G. Shchur5, N.Yu. Lashch2,5, N.F. Popova5,2, E.I. Gusev2, V.V. Bashinskaya2, D.V. Lvov3, A.V. Favorov3,4, M.F. Ochs4, O.O. Favorova1,2* Pharmacogenomics of Multiple Sclerosis: Association of Immune Response Gene Polymorphisms with Copaxone Treatment Efficacy 1Russian Research-and-Production Center, Ministry of Health, Moscow, 121552 Russia2Russian State Medical University, Moscow, 117437 Russia 3State Research Center GosNIIGenetika, Moscow, 117545 Russia 4Oncology Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, 21205, USА 5Moscow City Multiple Sclerosis Center, 127018 Russia *smedi@rambler.ru Received - 2010-12-15; Accepted - 2011-01-31 A complex association analysis of copaxone (glatiramer acetate) immunotherapy efficacy with allelic polymorphism of the number of immune response genes, including the genes for interferon β (IFNB1), transforming growth factor β1 (TGFB1), interferon γ (IFNG), tumor necrosis factor (TNF), interferon α/β receptor 1 (IFNAR1), CC chemokine receptor 5 (CCR5), interleukin 7 receptor subunit α (IL7RA), cytotoxic T-lymphocyte antigen 4 (CTLA4), and HLA class II histocompatibility antigen β chain (DRB1), was performed using the APSampler algorithm for 285 multiple sclerosis patients of Russian ethnicity. The results demonstrate that the polymorphic variants of CCR5, DRB1, IFNG, TGFB1, IFNAR1, IL7RA, and, possibly, TNF and CTLA4 contribute to the copaxone treatment response. Single alleles of CCR5 and DRB1 genes were reliably associated with treatment efficacy. Allelic variants of the other genes exerted a weaker, though still reliable, effect on the copaxone treatment response, but as part of bi- and triallelic combinations only. The study may provide a basis for a prognostic test allowing an individual choice of immune-modulating treatment for a patient with multiple sclerosis. pharmacogenomics, human, multiple sclerosis, copaxone, glatiramer acetate, Russians, autoimmune inflammation, cytokines, DNA, genes, SNP, PCR, APSampler |
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