Patricia Moya1,2, Juliana Salazar3,4, María Jesús Arranz5, César Díaz-Torné1, Elisabeth del Río3, Jordi Casademont1, Hèctor Corominas6, Montserrat Baiget3,4. 1. Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona. 2. Faculty of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona. 3. Genetics Department, Hospital de la Santa Creu i Sant Pau, Barcelona. 4. U705, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid. 5. Fundació Docència i Recerca Mutua Terrassa, Terrassa. 6. Rheumatology Department, Hospital Moisès Broggi, Sant Joan Despí, Barcelona.
Abstract
BACKGROUND: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. AIM: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. PATIENTS & METHODS: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. RESULTS: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). CONCLUSION: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.
BACKGROUND:Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. AIM: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RApatients receiving MTX. PATIENTS & METHODS: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. RESULTS: We studied 194 RApatients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGSrs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). CONCLUSION:FPGS and ABCB1 genetic variants can influence the outcome in RApatients receiving MTX monotherapy.
Authors: Dmitry S Mikhaylenko; Marina V Nemtsova; Irina V Bure; Ekaterina B Kuznetsova; Ekaterina A Alekseeva; Vadim V Tarasov; Alexander N Lukashev; Marina I Beloukhova; Andrei A Deviatkin; Andrey A Zamyatnin Journal: Int J Mol Sci Date: 2020-07-11 Impact factor: 5.923