Allelic combinations of immune-response genes associated with glatiramer acetate treatment response in Russian multiple sclerosis patients

Ekaterina Y. Tsareva, Olga G. Kulakova, Alexey N. Boyko, Sergey G. Shchur, Dmitrijs Lvovs, Alexander V. Favorov, Evgeny I. Gusev, Koen Vandenbroeck, Olga O. Favorova

Research output: Contribution to journalArticle

Abstract

Background: Glatiramer acetate (GA) is widely used as a first-line disease-modifying treatment for multiple sclerosis (MS). However, a significant proportion of MS patient appears to experience modest benefit from GA-treatment. Genetic variants affecting the clinical response to GA are believed to be relevant as biomarkers of GA-treatment efficiency. Patients & methods: Nine polymorphisms in candidate genes were analyzed as possible determinants of GA response in 285 Russian MS patients. Special attention was given to identification of response-associated allelic combinations by means of the APSampler algorithm. Results: No significant associations were found for individual polymorphisms. Alleles DRB1*15, TGFB1*T, CCR5*d and IFNAR1*G were the components of the combinations, of which carriage was significantly higher in nonresponders than in responders. Carriers of the most significant combinations: DRB1*15 + TGFB1*T + CCR5*d + IFNAR1*G and DRB1*15 + TGFB1*T + CCR5*d (permutation p-values: 0.0056 and 0.013, respectively) had a 14 to 15-times increased risk of ineffective response to GA therapy. Discussion: The results suggest that the influence of immune-response genes on GA-induced response has a polygenic nature. The data are interpreted as evidence of additive and epistatic influences of the genes on GA efficiency for MS treatment. Original submitted 21 June 2011; Revision submitted 31 August 201.

Original languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalPharmacogenomics
Volume13
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • APSampler
  • Copaxone
  • Cytokines
  • Glatiramer acetate
  • Multiple sclerosis
  • Pharmacogenomics
  • Polymorphism
  • SNP

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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  • Cite this

    Tsareva, E. Y., Kulakova, O. G., Boyko, A. N., Shchur, S. G., Lvovs, D., Favorov, A. V., Gusev, E. I., Vandenbroeck, K., & Favorova, O. O. (2012). Allelic combinations of immune-response genes associated with glatiramer acetate treatment response in Russian multiple sclerosis patients. Pharmacogenomics, 13(1), 43-53. https://doi.org/10.2217/pgs.11.136