title: Relationship between dimethylarginine dimethylaminohydrolase gene variants and asymmetric dimethylarginine in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  The aim of our study was to determine whether Dimethylarginine Dimethylaminohydrolase (DDAH) 1 and 2 gene polymorphisms - the main enzyme involved in ADMA degradation - are associated with high Asymmetric Dimethylarginine (ADMA) levels in Rheumatoid Arthritis (RA).
  
  
  METHODS
  Serum ADMA levels were measured in 201 individuals with RA [155 females median age 67 (59-73)]. Four tag SNPs in DDAH1 gene and 2 in the DDAH2 gene were genotyped by using the LightCycler™ System. ADMA was initially compared across the genetic variables using one-way ANOVA and then multivariate analysis examined each of the genes after adjustment for parameters of systemic inflammation and insulin resistance, namely erythrocyte sedimentation rate (ESR) and homeostatic model assessment (HOMA), which we have previously shown affect ADMA levels in RA.
  
  
  RESULTS
  No significant relationship between DDAH genetic variables and ADMA levels was established in ANOVA analysis. Multivariate model adjusted for age, HOMA and ESR did not demonstrate any significant association between DDAH variants and ADMA.
  
  
  CONCLUSIONS
  The results of our study give no evidence to suggest that increased ADMA levels in RA relate to DDAH genetic polymorphisms. Better understanding of disease-related factors and their interactions with traditional CV risk factors may represent mechanisms responsible for ADMA accumulation in this population.
authors.affiliation: Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley DY1 2HQ, UK. Electronic address: dimitroul@hotmail.com.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Dimitroulas
authors.affiliation: Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley DY1 2HQ, UK; School of Sport, Health and Exercise Sciences, Bangor University, George Building, Bangor, Gwynedd, Wales LL57 2PZ, UK.
authors.forename: Aamer
authors.initials: A
authors.lastname: Sandoo
authors.affiliation: Wolfson Computer Laboratory, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham B15 2WB, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hodson
authors.affiliation: Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley DY1 2HQ, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Smith
authors.affiliation: National Heart and Lung Institute, Imperial College London, UK.
authors.forename: Vasileios F
authors.initials: VF
authors.lastname: Panoulas
authors.affiliation: Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley DY1 2HQ, UK; Arthritis Research UK Epidemiology Unit, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: George D
authors.initials: GD
authors.lastname: Kitas
mesh_terms: D000368:Aged; D000581:Amidohydrolases / Q000235:genetics*; D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase
keywords: ADMA; CV disease; DDAH; Rheumatoid arthritis