title: Genetic polymorphisms, their allele combinations and IFN-beta treatment response in Irish multiple sclerosis patients.
abstract: BACKGROUND
  IFN-beta is widely used as first-line immunomodulatory treatment for multiple sclerosis. Response to treatment is variable (30-50% of patients are nonresponders) and requires a long treatment duration for accurate assessment to be possible. Information about genetic variations that predict responsiveness would allow appropriate treatment selection early after diagnosis, improve patient care, with time saving consequences and more efficient use of resources.
  
  
  METHODS
  We analyzed 61 SNPs in 34 candidate genes as possible determinants of IFN-beta response in Irish multiple sclerosis patients. Particular emphasis was placed on the exploration of combinations of allelic variants associated with response to therapy by means of a Markov chain Monte Carlo-based approach (APSampler).
  
  
  RESULTS
  The most significant allelic combinations, which differed in frequency between responders and nonresponders, included JAK2-IL10RB-GBP1-PIAS1 (permutation p-value was p(perm) = 0.0008), followed by JAK2-IL10-CASP3 (p(perm) = 0.001).
  
  
  CONCLUSIONS
  The genetic mechanism of response to IFN-beta is complex and as yet poorly understood. Data mining algorithms may help in uncovering hidden allele combinations involved in drug response versus nonresponse.
authors: University of South Australia, Adelaide, Australia.
authors: Catherine
authors: C
authors: O'Doherty
authors: Alexander
authors: A
authors: Favorov
authors: Shirley
authors: S
authors: Heggarty
authors: Colin
authors: C
authors: Graham
authors: Olga
authors: O
authors: Favorova
authors: Michael
authors: M
authors: Ochs
authors: Stanley
authors: S
authors: Hawkins
authors: Michael
authors: M
authors: Hutchinson
authors: Killian
authors: K
authors: O'Rourke
authors: Koen
authors: K
authors: Vandenbroeck
mesh_terms: D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D007494:Ireland; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D016899:Interferon-beta