title: Allelic combinations of immune-response genes associated with glatiramer acetate treatment response in Russian multiple sclerosis patients.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Russian State Medical University, Moscow, Russia. kateritsa@gmail.com
authors: Ekaterina Y
authors: EY
authors: Tsareva
authors: Olga G
authors: OG
authors: Kulakova
authors: Alexey N
authors: AN
authors: Boyko
authors: Sergey G
authors: SG
authors: Shchur
authors: Dmitrijs
authors: D
authors: Lvovs
authors: Alexander V
authors: AV
authors: Favorov
authors: Evgeny I
authors: EI
authors: Gusev
authors: Koen
authors: K
authors: Vandenbroeck
authors: Olga O
authors: OO
authors: Favorova
mesh_terms: D000328:Adult; D000483:Alleles; D054316:Biomarkers, Pharmacological / Q000097:blood; D004843:Epistasis, Genetic; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics; D056726:Genetic Association Studies; D000068717:Glatiramer Acetate; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics; D010455:Peptides / Q000627:therapeutic use*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D054316:Biomarkers, Pharmacological; D059811:HLA-DRB1 Chains; C507964:IFNAR1 protein, human; D010455:Peptides; D019713:Receptors, CCR5; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D053633:Receptor, Interferon alpha-beta; D000068717:Glatiramer Acetate