title: Associations between asymmetric dimethylarginine, homocysteine, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in rheumatoid arthritis.
abstract: OBJECTIVE
  The aim of our study was to determine whether asymmetric dimethylarginine (ADMA) levels are associated with homocysteine (Hcy) and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene variants in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Serum ADMA and Hcy levels were measured in 201 RA individuals [155 (77.1%) females, median age 67 years (interquartile range 59-73)]. The MTHFR C677T polymorphism was assessed by using the LightCyclerTM System. Initially, ADMA was compared across the categories of MTHFR using a one-way analysis of variance (ANOVA), followed by a multivariate model, which accounted for Hcy, age, erythrocyte sedimentation rate (ESR), and homeostatic model assessment (HOMA).
  
  
  RESULTS
  In univariable analysis, ADMA differed significantly across the categories of MTHFR (p = 0.037). Patients with the MTHFR 677TT genotype had the highest ADMA levels, with a mean of 0.62 (SE = 0.03), significantly higher than either those patients carrying the MTHFR 677CT (0.55, SE = 0.01) or the MTHFR 677CC (0.55, SE = 0.01) genotype (p = 0.042) in both cases. In the multivariable model, Hcy (p = 0.022) and ESR (p < 0.001) were found to have significant positive associations with ADMA but the relationship between MTHFR gene variants and ADMA was found to be non-significant (p = 0.102).
  
  
  CONCLUSIONS
  Hcy and ADMA are significantly associated in RA. It is plausible that abnormal Hcy metabolism plays an important role in premature atherosclerosis in RA by promoting ADMA accumulation and leading to the derangement of vascular haemostasis.
authors.affiliation: a Department of Rheumatology , Dudley Group of Hospitals NHS Trust, Russells Hall Hospital , Dudley , West Midlands , UK.
authors.forename: T
authors.initials: T
authors.lastname: Dimitroulas
authors.affiliation: a Department of Rheumatology , Dudley Group of Hospitals NHS Trust, Russells Hall Hospital , Dudley , West Midlands , UK.|b School of Sport, Health and Exercise Sciences , Bangor University , Bangor , Gwynedd, Wales , UK.
authors.forename: A
authors.initials: A
authors.lastname: Sandoo
authors.affiliation: c Wolfson Computer Laboratory , University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham , UK.
authors.forename: J
authors.initials: J
authors.lastname: Hodson
authors.affiliation: a Department of Rheumatology , Dudley Group of Hospitals NHS Trust, Russells Hall Hospital , Dudley , West Midlands , UK.
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.affiliation: a Department of Rheumatology , Dudley Group of Hospitals NHS Trust, Russells Hall Hospital , Dudley , West Midlands , UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Douglas
authors.affiliation: a Department of Rheumatology , Dudley Group of Hospitals NHS Trust, Russells Hall Hospital , Dudley , West Midlands , UK.|d Arthritis Research UK Epidemiology Unit , University of Manchester , Manchester , UK.
authors.forename: G D
authors.initials: GD
authors.lastname: Kitas
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic
chemical_list: D006710:Homocysteine; C018524:N,N-dimethylarginine; D001120:Arginine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)