Pharmacogenomics of multiple sclerosis: Association of immune response gene polymorphisms with copaxone treatment efficacy

E. Yu Tsareva; O. G. Kulakova; O. Yu Makarycheva; A. N. Boyko; S. G. Shchur; N. Yu Lashch; N. F. Popova; E. I. Gusev; V. V. Bashinskaya; D. V. Lvov; A. V. Favorov; M. F. Ochs; O. O. Favorova

doi:10.1134/S0026893311060185

Pharmacogenomics of multiple sclerosis: Association of immune response gene polymorphisms with copaxone treatment efficacy

E. Yu Tsareva, O. G. Kulakova, O. Yu Makarycheva, A. N. Boyko, S. G. Shchur, N. Yu Lashch, N. F. Popova, E. I. Gusev, V. V. Bashinskaya, D. V. Lvov, A. V. Favorov, M. F. Ochs, O. O. Favorova

School of Medicine

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	886-893
Number of pages	8
Journal	Molecular Biology
Volume	45
Issue number	6
DOIs	https://doi.org/10.1134/S0026893311060185
State	Published - Dec 2011

Keywords

APSampler
DNA
PCR
Russians
SNP
autoimmune inflammation
copaxone
cytokines
genes
glatiramer acetate
human
multiple sclerosis
pharmacogenomics

ASJC Scopus subject areas

Biophysics
Structural Biology

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10.1134/S0026893311060185

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Tsareva, E. Y., Kulakova, O. G., Makarycheva, O. Y., Boyko, A. N., Shchur, S. G., Lashch, N. Y., Popova, N. F., Gusev, E. I., Bashinskaya, V. V., Lvov, D. V., Favorov, A. V., Ochs, M. F., & Favorova, O. O. (2011). Pharmacogenomics of multiple sclerosis: Association of immune response gene polymorphisms with copaxone treatment efficacy. Molecular Biology, 45(6), 886-893. https://doi.org/10.1134/S0026893311060185

Tsareva, EY, Kulakova, OG, Makarycheva, OY, Boyko, AN, Shchur, SG, Lashch, NY, Popova, NF, Gusev, EI, Bashinskaya, VV, Lvov, DV, Favorov, AV, Ochs, MF & Favorova, OO 2011, 'Pharmacogenomics of multiple sclerosis: Association of immune response gene polymorphisms with copaxone treatment efficacy', Molecular Biology, vol. 45, no. 6, pp. 886-893. https://doi.org/10.1134/S0026893311060185

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title = "Pharmacogenomics of multiple sclerosis: Association of immune response gene polymorphisms with copaxone treatment efficacy",

abstract = "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.",

keywords = "APSampler, DNA, PCR, Russians, SNP, autoimmune inflammation, copaxone, cytokines, genes, glatiramer acetate, human, multiple sclerosis, pharmacogenomics",

author = "Tsareva, {E. Yu} and Kulakova, {O. G.} and Makarycheva, {O. Yu} and Boyko, {A. N.} and Shchur, {S. G.} and Lashch, {N. Yu} and Popova, {N. F.} and Gusev, {E. I.} and Bashinskaya, {V. V.} and Lvov, {D. V.} and Favorov, {A. V.} and Ochs, {M. F.} and Favorova, {O. O.}",

note = "Funding Information: ACKNOWLEDGMENTS This work was supported by the Russian Founda tion for Basic Research (project no. 08 04 01834 a) and a UEPHA*MS FP7 Marie Curie Initial Training Network program.",

year = "2011",

month = dec,

doi = "10.1134/S0026893311060185",

language = "English (US)",

volume = "45",

pages = "886--893",

journal = "Molecular Biology",

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TY - JOUR

T1 - Pharmacogenomics of multiple sclerosis

T2 - Association of immune response gene polymorphisms with copaxone treatment efficacy

AU - Tsareva, E. Yu

AU - Kulakova, O. G.

AU - Makarycheva, O. Yu

AU - Boyko, A. N.

AU - Shchur, S. G.

AU - Lashch, N. Yu

AU - Popova, N. F.

AU - Gusev, E. I.

AU - Bashinskaya, V. V.

AU - Lvov, D. V.

AU - Favorov, A. V.

AU - Ochs, M. F.

AU - Favorova, O. O.

N1 - Funding Information: ACKNOWLEDGMENTS This work was supported by the Russian Founda tion for Basic Research (project no. 08 04 01834 a) and a UEPHA*MS FP7 Marie Curie Initial Training Network program.

PY - 2011/12

Y1 - 2011/12

N2 - 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.

AB - 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.

KW - APSampler

KW - DNA

KW - PCR

KW - Russians

KW - SNP

KW - autoimmune inflammation

KW - copaxone

KW - cytokines

KW - genes

KW - glatiramer acetate

KW - human

KW - multiple sclerosis

KW - pharmacogenomics

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DO - 10.1134/S0026893311060185

M3 - Article

AN - SCOPUS:82655189351

SN - 0026-8933

VL - 45

SP - 886

EP - 893

JO - Molecular Biology

JF - Molecular Biology

IS - 6

ER -

Pharmacogenomics of multiple sclerosis: Association of immune response gene polymorphisms with copaxone treatment efficacy

Abstract

Keywords

ASJC Scopus subject areas

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