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

Pharmacogenomics. 2017 Nov;18(17):1563-1574. doi: 10.2217/pgs-2017-0058. Epub 2017 Nov 2.

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.

MeSH terms

  • Adult
  • Alleles
  • Female
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Genotype
  • Glatiramer Acetate / therapeutic use*
  • Humans
  • Male
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / genetics*
  • Pharmacogenetics / methods
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • Glatiramer Acetate