title: Lack of association of variants previously associated with anti-TNF medication response in rheumatoid arthritis patients: results from a homogeneous Greek population.
abstract: Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. However, a significant subset of patients does not respond to anti-TNF agents, for reasons that are still unknown. The aim of this study was to validate five single nucleotide polymorphisms (SNPs) of PTPRC, CD226, AFF3, MyD88 and CHUK gene loci that have previously been reported to predict anti-TNF outcome. In addition, two markers of RA susceptibility, namely TRAF1/C5 and STAT4 were assessed, in a cohort of anti-TNF-treated RA patients, from the homogeneous Greek island of Crete, Greece. The RA patient cohort consisted of 183 patients treated with either of 3 anti-TNF biologic agents (infliximab, adalimumab and etanercept) from the Clinic of Rheumatology of the University Hospital of Crete. The SNPs were genotyped by TaqMan assays or following the Restriction Fragments Length Polymorphisms (RFLPs) approach. Disease activity score in 28 joints (DAS28) at baseline and after 6 months were available for all patients and analysis of good versus poor response at 6 months was performed for each SNP. None of the 7 genetic markers correlated with treatment response. We conclude that the gene polymorphisms under investigation are not strongly predictive of anti-TNF response in RA patients from Greece.
authors.affiliation: Laboratory of Molecular Medicine and Human Genetics, Medical School of Crete, Heraklion, Crete, Greece.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Zervou
authors.forename: Efsevia
authors.initials: E
authors.lastname: Myrthianou
authors.forename: Irene
authors.initials: I
authors.lastname: Flouri
authors.forename: Darren
authors.initials: D
authors.lastname: Plant
authors.forename: Gregory
authors.initials: G
authors.lastname: Chlouverakis
authors.forename: Francesc
authors.initials: F
authors.lastname: Castro-Giner
authors.forename: Panayiota
authors.initials: P
authors.lastname: Rapsomaniki
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Boumpas
authors.forename: Prodromos
authors.initials: P
authors.lastname: Sidiropoulos
authors.forename: George N
authors.initials: GN
authors.lastname: Goulielmos
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000068800:Etanercept; D005260:Female; D018703:Founder Effect; D056426:Genetic Loci; D005819:Genetic Markers; D006115:Greece; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D005819:Genetic Markers; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept
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