title: Decreased expression of methylene tetrahydrofolate reductase (MTHFR) gene in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Impairment of methylene tetrahydrofolate reductase (MTHFR), a key enzyme in the folate metabolism, results in an elevated plasma level of homocysteine, considered an independent risk factor for cardiovascular (CV) disease. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased risk of CV death. Polymorphisms in the MTHFR gene increase the frequency of CV disease in RA. The aim of this study was to determine the expression of MTHFR gene in patients with RA, with and without ischaemic heart disease (IHD).
  
  
  METHODS
  Relative expression of MTHFR gene and beta-actin and GAPDH as housekeeping genes was quantified by quantitative real-time polymerase chain reaction. It was analysed by the comparative Ct (threshold cycle) method in peripheral blood from 26 Spanish patients with RA (12 with IHD and 14 without IHD) and 10 healthy controls. MTHFR expression level in RA patients was also assessed according to disease activity, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies status.
  
  
  RESULTS
  MTHFR expression was significantly reduced in patients with RA compared to controls (fold change = 0.85, p=0.029). It was especially true for RA patients with IHD (fold change= 0.79, p=0.021). However, no statistically significant relationship between MTHFR expression level in patients with RA and DAS28 CRP, DAS28 ESR, RF and anti-CCP status was observed.
  
  
  CONCLUSIONS
  Patients with RA, in particular those with IHD, show a decreased expression of the MTHFR gene. This may support a potential implication of the transcriptional regulation of MTHFR in the pathogenesis of RA.
authors: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain.
authors: Sara
authors: S
authors: Remuzgo-Martínez
authors: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain.
authors: Fernanda
authors: F
authors: Genre
authors: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain.
authors: Raquel
authors: R
authors: López-Mejías
authors: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain.
authors: Begoña
authors: B
authors: Ubilla
authors: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain.
authors: Veronica
authors: V
authors: Mijares
authors: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain.
authors: Trinitario
authors: T
authors: Pina
authors: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain.
authors: Alfonso
authors: A
authors: Corrales
authors: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain.
authors: Ricardo
authors: R
authors: Blanco
authors: Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain.
authors: Javier
authors: J
authors: Martín
authors: Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVAL, Santander, Spain.
authors: Javier
authors: J
authors: Llorca
authors: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain. miguelaggay@hotmail.com.
authors: Miguel Á
authors: MÁ
authors: González-Gay
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000201:enzymology; D010456:Peptides, Cyclic / Q000276:immunology; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index; D013030:Spain
chemical_list: D015415:Biomarkers; D010456:Peptides, Cyclic; D012333:RNA, Messenger; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)