Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis: The impact of genome-wide association studies identified disease risk loci

Olga Kulakova; Vitalina Bashinskaya; Ivan Kiselev; Natalia Baulina; Ekaterina Tsareva; Ruslan Nikolaev; Maxim Kozin; Sergey Shchur; Alexander Favorov; Alexey Boyko; Olga Favorova

doi:10.2217/pgs-2017-0058

Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis: The impact of genome-wide association studies identified disease risk loci

Olga Kulakova, Vitalina Bashinskaya, Ivan Kiselev, Natalia Baulina, Ekaterina Tsareva, Ruslan Nikolaev, Maxim Kozin, Sergey Shchur, Alexander Favorov, Alexey Boyko, Olga Favorova

School of Medicine

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

6 Scopus citations

Abstract

Aim: Association analysis of genome-wide association studies (GWAS) identified multiple sclerosis (MS) risk genetic variants with glatiramer acetate (GA) treatment efficacy. Patients & methods: SNPs in 17 GWAS-identified immune response loci were analyzed in 296 Russian MS patients as possible markers of optimal GA treatment response for at least 2 years. Results: Alleles/genotypes of EOMES, CLEC16A, IL22RA2, PVT1 and HLA-DRB1 were associated by themselves with event-free phenotype during GA treatment for at least 2 years (p _f = 0.032-0.00092). The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level (p _f = 0.0060-1.1 × 10^- ⁵). The epistasic interactions or additive effects were observed between the components of the identified biallelic combinations. Conclusion: We pinpointed the involvement of several GWAS-identified MS risk loci in GA therapy efficacy. These findings may be aggregated to predict the optimal GA response in MS patients.

Original language	English (US)
Pages (from-to)	1563-1574
Number of pages	12
Journal	Pharmacogenomics
Volume	18
Issue number	17
DOIs	https://doi.org/10.2217/pgs-2017-0058
State	Published - Nov 2017

Keywords

GWAS
SNP
biomarker
copaxone
epistasis
glatiramer acetate
multiple sclerosis
pharmacogenomics
polymorphism

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

Access to Document

10.2217/pgs-2017-0058

Cite this

Kulakova, O., Bashinskaya, V., Kiselev, I., Baulina, N., Tsareva, E., Nikolaev, R., Kozin, M., Shchur, S., Favorov, A., Boyko, A., & Favorova, O. (2017). Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis: The impact of genome-wide association studies identified disease risk loci. Pharmacogenomics, 18(17), 1563-1574. https://doi.org/10.2217/pgs-2017-0058

Kulakova, O, Bashinskaya, V, Kiselev, I, Baulina, N, Tsareva, E, Nikolaev, R, Kozin, M, Shchur, S, Favorov, A, Boyko, A & Favorova, O 2017, 'Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis: The impact of genome-wide association studies identified disease risk loci', Pharmacogenomics, vol. 18, no. 17, pp. 1563-1574. https://doi.org/10.2217/pgs-2017-0058

@article{2f117905391040209700edb6ffd48556,

title = "Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis: The impact of genome-wide association studies identified disease risk loci",

abstract = "Aim: Association analysis of genome-wide association studies (GWAS) identified multiple sclerosis (MS) risk genetic variants with glatiramer acetate (GA) treatment efficacy. Patients & methods: SNPs in 17 GWAS-identified immune response loci were analyzed in 296 Russian MS patients as possible markers of optimal GA treatment response for at least 2 years. Results: Alleles/genotypes of EOMES, CLEC16A, IL22RA2, PVT1 and HLA-DRB1 were associated by themselves with event-free phenotype during GA treatment for at least 2 years (p f = 0.032-0.00092). The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level (p f = 0.0060-1.1 × 10- 5). The epistasic interactions or additive effects were observed between the components of the identified biallelic combinations. Conclusion: We pinpointed the involvement of several GWAS-identified MS risk loci in GA therapy efficacy. These findings may be aggregated to predict the optimal GA response in MS patients.",

keywords = "GWAS, SNP, biomarker, copaxone, epistasis, glatiramer acetate, multiple sclerosis, pharmacogenomics, polymorphism",

author = "Olga Kulakova and Vitalina Bashinskaya and Ivan Kiselev and Natalia Baulina and Ekaterina Tsareva and Ruslan Nikolaev and Maxim Kozin and Sergey Shchur and Alexander Favorov and Alexey Boyko and Olga Favorova",

note = "Funding Information: This study was funded by Russian Foundation for Basic Research according to the research project no. 17-00-00295 (17-00-00206 and 17-00-00208) and government contract with Pirogov Russian National Research Medical University (2015–2017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: {\textcopyright} 2017 Future Medicine Ltd. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

year = "2017",

month = nov,

doi = "10.2217/pgs-2017-0058",

language = "English (US)",

volume = "18",

pages = "1563--1574",

journal = "Pharmacogenomics",

issn = "1462-2416",

publisher = "Future Medicine Ltd.",

number = "17",

}

TY - JOUR

T1 - Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis

T2 - The impact of genome-wide association studies identified disease risk loci

AU - Kulakova, Olga

AU - Bashinskaya, Vitalina

AU - Kiselev, Ivan

AU - Baulina, Natalia

AU - Tsareva, Ekaterina

AU - Nikolaev, Ruslan

AU - Kozin, Maxim

AU - Shchur, Sergey

AU - Favorov, Alexander

AU - Boyko, Alexey

AU - Favorova, Olga

N1 - Funding Information: This study was funded by Russian Foundation for Basic Research according to the research project no. 17-00-00295 (17-00-00206 and 17-00-00208) and government contract with Pirogov Russian National Research Medical University (2015–2017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: © 2017 Future Medicine Ltd. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2017/11

Y1 - 2017/11

N2 - Aim: Association analysis of genome-wide association studies (GWAS) identified multiple sclerosis (MS) risk genetic variants with glatiramer acetate (GA) treatment efficacy. Patients & methods: SNPs in 17 GWAS-identified immune response loci were analyzed in 296 Russian MS patients as possible markers of optimal GA treatment response for at least 2 years. Results: Alleles/genotypes of EOMES, CLEC16A, IL22RA2, PVT1 and HLA-DRB1 were associated by themselves with event-free phenotype during GA treatment for at least 2 years (p f = 0.032-0.00092). The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level (p f = 0.0060-1.1 × 10- 5). The epistasic interactions or additive effects were observed between the components of the identified biallelic combinations. Conclusion: We pinpointed the involvement of several GWAS-identified MS risk loci in GA therapy efficacy. These findings may be aggregated to predict the optimal GA response in MS patients.

AB - Aim: Association analysis of genome-wide association studies (GWAS) identified multiple sclerosis (MS) risk genetic variants with glatiramer acetate (GA) treatment efficacy. Patients & methods: SNPs in 17 GWAS-identified immune response loci were analyzed in 296 Russian MS patients as possible markers of optimal GA treatment response for at least 2 years. Results: Alleles/genotypes of EOMES, CLEC16A, IL22RA2, PVT1 and HLA-DRB1 were associated by themselves with event-free phenotype during GA treatment for at least 2 years (p f = 0.032-0.00092). The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level (p f = 0.0060-1.1 × 10- 5). The epistasic interactions or additive effects were observed between the components of the identified biallelic combinations. Conclusion: We pinpointed the involvement of several GWAS-identified MS risk loci in GA therapy efficacy. These findings may be aggregated to predict the optimal GA response in MS patients.

KW - GWAS

KW - SNP

KW - biomarker

KW - copaxone

KW - epistasis

KW - glatiramer acetate

KW - multiple sclerosis

KW - pharmacogenomics

KW - polymorphism

UR - http://www.scopus.com/inward/record.url?scp=85034570783&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034570783&partnerID=8YFLogxK

U2 - 10.2217/pgs-2017-0058

DO - 10.2217/pgs-2017-0058

M3 - Article

C2 - 29095108

AN - SCOPUS:85034570783

SN - 1462-2416

VL - 18

SP - 1563

EP - 1574

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 17

ER -

Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis: The impact of genome-wide association studies identified disease risk loci

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this