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A7.15 Lack of Association of Variants Previously Associated with Anti-TNF Medication Response in Rheumatoid Arthritis Patients: Results from a Homogeneous Greek Population
  1. MI Zervou1,
  2. P Sidiropoulos2,
  3. E Myrthianou1,
  4. I Flouri2,
  5. D Plant3,
  6. P Rapsomaniki2,
  7. A Barton3,
  8. DT Boumpas4,5,
  9. GN Goulielmos1
  1. 1Laboratory of Molecular Medicine and Human Genetics, Medical School of Crete, Greece
  2. 2Department of Rheumatology, Clinical Immunology and Allergy, University Hospital of Heraklion, Greece
  3. 3
  4. 4Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Heraklion, Greece
  5. 5Medical School, University of Athens, Greece

Abstract

Background Treatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in about 50–60% of the patients. However, a significant subset of patients does not respond to the medication, for reasons that are still unknown.

Aim To validate five genetic factors, previously suggested to predict anti-TNF outcome, and two additional RA-associated SNPs in a cohort of anti-TNF–treated RA patients, from the homogeneous Greek island of Crete, Greece.

Materials and Methods The RA sample set consisted of 183 patients treated with the 3 anti-TNF biologic agents (Infliximab, Adalimumab and Etanercept) from the Clinic of Rheumatology of the University Hospital of Crete. Single Nucleotide Polymorphisms (SNPs) markers, namely PTPRC Rs10919563, CD226 Rs763361, AFF3 Rs10865035, MyD88 Rs7744 and CHUK Rs11591741 SNPs were genotyped with Taqman primer-probe sets, while TRAF1/C5 Rs10818488 and STAT4 Rs7574865 genotyped following the Restriction Fragments Length Polymorphisms (RFLPs) approach. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and the statistical difference in allele distribution was assessed by means of x2 test or Fisher’s exact test.

Results We tested various demographic factors such as age, sex, and concomitant medications for correlation with treatment response to biologics. Disease activity score in 28 joints (DAS28) at baseline and after 6 months were available for these patients and analysis of good versus poor response at 6 months was performed for each SNP. In this cohort of patients, consisting predominantly of patients on infliximab (66.67%), none of the 7 successfully genotyped markers demonstrated association with treatment response.

Conclusions We conclude that the gene polymorphisms under investigation are not strongly predictive of anti-TNF response in RA patients from Crete (Greece). However, larger studies are needed to definitively exclude association of the SNPs under investigation in the Greek population and this study needs to be extended by involving more RA-associated SNPs in an attempt to predict anti-TNF outcome in Greece.

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