title: Multidrug resistance protein-1 expression, function and polymorphisms in patients with rheumatoid arthritis not responding to methotrexate.
abstract: OBJECTIVE
  To study the expression, function and polymorphism of MDR-1 protein on the peripheral blood lymphocytes in patients with RA following treatment with MTX and its relationship with response to therapy.
  
  
  METHODS
  RA patients naïve to MTX/DMARD- and glucocorticoid were enrolled. Expression and function of MDR-1 was carried out by flow cytometry at baseline and after 4 months of therapy. MDR-1 expression was measured by relative fluorescence intensities and percentage of positive cells. MDR-1 function was assessed by Rhodamine efflux in presence or absence of verapamil. Patients with reduction in disease activity score 28 ≥1.2 were defined as responders and <1.2 as non-responders. Three single nucleotide polymorphisms in MDR-1 gene, 3435T, 1236T and 2677T/A were studied.
  
  
  RESULTS
  Fifty-two patients of RA were grouped into responders (n = 41), and non-responders (n = 11) as per the defined criteria. There was no difference between the groups in terms of age, sex ratio or duration of illness, MTX dose and follow-up duration. The expression and function of the MDR-1 protein reduced significantly in the responder group after the treatment with MTX when compared to the baseline evaluation. The decrease was significant when compared to the non-responders at the fourth month. MDR-1 expression and function either increased or remained the same in the non-responder group after treatment with MTX. MTX unresponsiveness was not related to any of the three polymorphisms studied.
  
  
  CONCLUSIONS
  Persistent expression and function of MDR-1 identifies a subset of RA patients not responding to MTX. Its early recognition may help in appropriately modulating therapy.
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Shiva
authors.initials: S
authors.lastname: Prasad
authors.forename: Deepak
authors.initials: D
authors.lastname: Tripathi
authors.forename: Mohit K
authors.initials: MK
authors.lastname: Rai
authors.forename: Suraksha
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
authors.forename: Vikas
authors.initials: V
authors.lastname: Agarwal
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017211:Treatment Failure
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018501:Antirheumatic Agents; D008727:Methotrexate
keywords: Rhodamine dye exclusion; failure; methotrexate; multidrug resistance protein-1; peripheral blood lymphocytes; rheumatoid arthritis