Wefa Boughrara1,2, Ahmed Benzaoui3, Meriem Aberkane4, Fatima Zohra Moghtit5, Samia Dorgham5, Aicha Sarah Lardjam-Hetraf5, Hadjer Ouhaibi-Djellouli5, Elisabeth Petit Teixeira6, Abdallah Boudjema5. 1. Laboratoire de génétique moléculaire et cellulaire, Université des sciences et de la technologie d'Oran Mohamed Boudiaf (USTO-MB), BP 1505, El-M'naouar, 31000, Oran, Algeria. wefaboughrara@gmail.com. 2. Ecole préparatoire en science de la nature et de la vie d'Oran (EPSNVO), Oran, Algeria. wefaboughrara@gmail.com. 3. Service de Rhumatologie, Centre Hospitalo-universitaire d'Oran (CHUO), Université d'Oran 1, Oran, Algeria. 4. Département de pharmacie, Université d'Oran 1, Oran, Algeria. 5. Laboratoire de génétique moléculaire et cellulaire, Université des sciences et de la technologie d'Oran Mohamed Boudiaf (USTO-MB), BP 1505, El-M'naouar, 31000, Oran, Algeria. 6. GenHotel-EA3886, Evry-Val d'Essonne University, Evry-Genopole, France.
Abstract
CONTEXT: The c.677 C > T and c.1298 A > C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene and c.3435 C > T polymorphism of ATP-Binding cassette B1 (ABCB1) gene are reported as pharmacogenetic markers, influencing the methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA) patients. OBJECTIVES: The aims of this study were to determine the relationship between these polymorphisms and clinical response and/or adverse drug reaction (ADRs) to MTX treatment. MATERIALS AND METHODS: The cohort of our study was composed of 110 RA patients of the West Algerian population. The clinical response was evaluated using the disease activity score 28 (DAS28) and the ADRs were collected after physical examination of patients. All samples were genotyped for theses polymorphisms by TaqMan® allelic discrimination assay. RESULTS: Based on EULAR criteria, 59.09% RA patients were responders and ADRs were observed in 40.9% patients. The frequency distribution of these three polymorphisms was similar between the responders and the non-responders. The same result was found on ADRs study and no significant difference of distribution between the presence of ADRs group and absence of ADRs group was observed. DISCUSSION: Our study joins the results that found in others population in the world. CONCLUSION: We have demonstrated, for the first time in the West Algerian population, that these polymorphisms were not predictive for clinical response and/or ADRs to MTX therapeutic outcome.
CONTEXT: The c.677 C > T and c.1298 A > C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene and c.3435 C > T polymorphism of ATP-Binding cassette B1 (ABCB1) gene are reported as pharmacogenetic markers, influencing the methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA) patients. OBJECTIVES: The aims of this study were to determine the relationship between these polymorphisms and clinical response and/or adverse drug reaction (ADRs) to MTX treatment. MATERIALS AND METHODS: The cohort of our study was composed of 110 RApatients of the West Algerian population. The clinical response was evaluated using the disease activity score 28 (DAS28) and the ADRs were collected after physical examination of patients. All samples were genotyped for theses polymorphisms by TaqMan® allelic discrimination assay. RESULTS: Based on EULAR criteria, 59.09% RApatients were responders and ADRs were observed in 40.9% patients. The frequency distribution of these three polymorphisms was similar between the responders and the non-responders. The same result was found on ADRs study and no significant difference of distribution between the presence of ADRs group and absence of ADRs group was observed. DISCUSSION: Our study joins the results that found in others population in the world. CONCLUSION: We have demonstrated, for the first time in the West Algerian population, that these polymorphisms were not predictive for clinical response and/or ADRs to MTX therapeutic outcome.
Authors: Guy Leschziner; Delilah Zabaneh; M Pirmohamed; Andrew Owen; Jane Rogers; Alison J Coffey; David J Balding; David B Bentley; Michael R Johnson Journal: Pharmacogenet Genomics Date: 2006-06 Impact factor: 2.089
Authors: R Takatori; K A Takahashi; D Tokunaga; T Hojo; M Fujioka; T Asano; T Hirata; Y Kawahito; Y Satomi; H Nishino; T Tanaka; Y Hirota; T Kubo Journal: Clin Exp Rheumatol Date: 2006 Sep-Oct Impact factor: 4.473
Authors: Wouter M Kooloos; Judith Am Wessels; Tahar van der Straaten; Cornelia F Allaart; Tom Wj Huizinga; Henk-Jan Guchelaar Journal: Pharmacogenomics Date: 2010-02 Impact factor: 2.533
Authors: Karina I Halilova; Elizabeth E Brown; Sarah L Morgan; S Louis Bridges; Min-Ho Hwang; Donna K Arnett; Maria I Danila Journal: Int J Rheumatol Date: 2012-07-09