Souhir Chaabane1, Meriam Messedi2, Rim Akrout3, Mariem Ben Hamad4, Mouna Turki2, Sameh Marzouk5, Leila Keskes4, Zouheir Bahloul5, Ahmed Rebai6, Fatma Ayedi2, Abdellatif Maalej4. 1. Laboratory of Human Molecular Genetics, Faculty of Medicine, Avenue Majida Boulila, 3029, Sfax, Tunisia. Chaabane.souhir@yahoo.fr. 2. UR "Molecular Bases of Human Diseases", Faculty of Medicine, Sfax, Tunisia. 3. Department of Rheumatology, University Hospital Hedi Chaker, Sfax, Tunisia. 4. Laboratory of Human Molecular Genetics, Faculty of Medicine, Avenue Majida Boulila, 3029, Sfax, Tunisia. 5. Department of Internal Medicine, University Hospital Hedi Chaker, Sfax, Tunisia. 6. Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology, Sfax, Tunisia.
Abstract
OBJECTIVES: The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R → 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients. METHODS: A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy > 15 µmol/L. RESULTS: MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07-4.57]; p = 0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p = 0.035). CONCLUSIONS: The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.
OBJECTIVES: The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFRC677T and A1298C), thymidylate synthase (TYMS 2R → 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients. METHODS: A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy > 15 µmol/L. RESULTS:MTHFRC677T polymorphism was associated with HHC in RApatients (multi-adjusted OR, 95% CI 2.18, [1.07-4.57]; p = 0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTXtoxicity (32.7 vs. 16.7%; p = 0.035). CONCLUSIONS: The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RApatients. HHC could be a useful marker of MTXtoxicity in RApatients.
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