title: Thymidylate synthase genetic polymorphism and plasma total homocysteine level in a group of Turkish patients with rheumatoid arthritis: relationship with disease activity and methotrexate toxicity.
abstract: BACKGROUND
  The polymorphism of thymidylate synthase (TS) gene and homocysteine are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine homocysteine levels and the frequency of TS gene triple repeat (TS3R) and double repeat (TS2R) polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity and disease activity.
  
  
  METHODS
  Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 ± 12.5 and 46.2 ± 13.4 years, were enrolled to the study. Demographic characteristics were obtained and number of patients with MTX-related adverse affects, were recorded in the patient group. The homocysteine levels and TS2R/TS3R polymorphisms of the TS gene were analyzed and the distribution of genotypes according to MTX toxicity and disease activity, were determined.
  
  
  RESULTS
  The demographic properties were similar between the patient and control subjects. Folic acid supplementation with a mean dose of 5mg folic acid/week, was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment. The frequency of TS2R and TS3R polymorphisms were found to be similar in the patient and control groups. TS2R and TS3R gene polymorphisms were found to be similar in patients with and without MTX-related adverse events. The mean homocysteine level was also similar in patients with and without TS gene polymorphism, but was found to be higher (12.45μmol/L vs 10.7μmol/L) in patients with MTX-related side effects than in patients without side effects. The mean level of homocysteine was correlated with levels of ESR in the patient group.
  
  
  CONCLUSIONS
  In conclusion, homocysteine levels might effect the disease activity and toxicity of MTX but 2R and 3R polymorphisms in the TS gene, were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible from the MTX toxicity in patients suffering from RA.
authors: Ankara Training and Research Hospital Clinic of Physical Medicine and Rehabilitation, Ancara, Turquia. Electronic address: pinarborman@gmail.com.
authors: Pınar
authors: P
authors: Borman
authors: Ankara Training and Research Hospital Clinic of Physical Medicine and Rehabilitation, Ancara, Turquia.
authors: Özgur
authors: Ö
authors: Taşbaş
authors: Departamento de Genética, Faculdade de Medicina, Ankara University, Ancara, Turquia.
authors: Halil
authors: H
authors: Karabulut
authors: Departamento de Genética, Faculdade de Medicina, Ankara University, Ancara, Turquia.
authors: Ajlan
authors: A
authors: Tukun
authors: Ankara Training and Research Hospital Clinic of Physical Medicine and Rehabilitation, Ancara, Turquia.
authors: Rezan
authors: R
authors: Yorgancıoğlu
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology*; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013940:Thymidylate Synthase / Q000235:genetics*; D014803:Vitamin B Complex / Q000008:administration & dosage
chemical_list: D018501:Antirheumatic Agents; D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid; D013940:Thymidylate Synthase; D008727:Methotrexate
keywords: Artrite reumatoide; Homocisteína; Homocystein; Methotrexate; Metotrexato; Polimorfismo; Polymorphism; Rheumatoid arthritis; Thymidylate synthase; Timidilato sintase