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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1563-1574
Number of pages12
JournalPharmacogenomics
Volume18
Issue number17
DOIs
StatePublished - Nov 1 2017

Keywords

  • biomarker
  • copaxone
  • epistasis
  • glatiramer acetate
  • GWAS
  • multiple sclerosis
  • pharmacogenomics
  • polymorphism
  • SNP

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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  • 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