[Pharmacogenomics of multiple sclerosis: association of immune response genes polymorphism with copaxone treatment efficacy].

Abstract

Complex association analysis of copaxone (glatiramer acetate) immunotherapy efficacy with allelic polymorphism in the number of immune response genes, which encode interferone beta (IFNB1), transforming growth factor beta1 (TGFB1), interferone gamma (IFNG), tumor necrosis factor (TNF), interferon alpha/beta receptor 1 (IFNAR1), CC chemokine receptor 5 (CCR5), interleukin 7 receptor alpha subunit (IL7RA), cytotoxic T-lymphocyte antigen 4 (CTLA4) and HLA class II histocompatibility antigen beta chain (DRB1) was performed with APSampler algorithm for 285 multiple sclerosis patients of Russian ethnicity. The results show evidence for the contribution of polymorphic variants in CCRS, DRB1, IFNG, TGFB1, IFNAR1, IL7RA and, probably, TNF and CTLA4 genes to copaxone treatment response. Single alleles of CCR5 and DRB1 genes are reliably associated with treatment efficacy. Carriage of allelic variants of other above mentioned genes contribute with reliable effect to copaxone treatment response as part of bi- and three-allelic combinations only. Present investigation may support basis toward the future possibility of prognostic test realization, which can provide a personal choice of immunomodulatory treatment for a patient with multiple sclerosis.

• Authors: E Iu Tsareva, O G Kulakova, O Iu Makarycheva, A N Boĭko, S G Shchur, N Iu Lashch, N F Popova, E I Gusev, V V Bashinskaia, D V L'vov, A V Favorov, M F Ochs, O O Favorova
• Journal: Molekuliarnaia biologiia (Mol Biol (Mosk)) 2011 Nov-Dec Vol. 45 Issue 6 Pg. 963-72 ISSN: 0026-8984 [Print] Russia (Federation)
• PMID: 22295566 (Publication Type: English Abstract, Journal Article)

Chemical References

• Adjuvants, Immunologic
• Biomarkers, Pharmacological
• CTLA-4 Antigen
• HLA-DRB1 Chains
• Interleukin-7 Receptor alpha Subunit
• Peptides
• Receptors, CCR5
• TNF protein, human
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• Glatiramer Acetate
• Interferon-beta
• Interferon-gamma

Topics

• Adjuvants, Immunologic (pharmacokinetics, therapeutic use)
• Biomarkers, Pharmacological
• CTLA-4 Antigen (genetics)
• Gene Frequency
• Genetic Association Studies
• Glatiramer Acetate
• HLA-DRB1 Chains (genetics)
• Humans
• Interferon-beta (genetics)
• Interferon-gamma (genetics)
• Interleukin-7 Receptor alpha Subunit (genetics)
• Multiple Sclerosis (drug therapy, genetics)
• Peptides (pharmacokinetics, therapeutic use)
• Polymorphism, Single Nucleotide
• Receptors, CCR5 (genetics)
• Transforming Growth Factor beta1 (genetics)
• Tumor Necrosis Factor-alpha (genetics)