title: Association analysis of nitric oxide synthases: NOS1, NOS2A and NOS3 genes, with multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a chronic inflammatory autoimmune disorder of the central nervous system.
  
  
  OBJECTIVE
  To explore the genetic basis of three nitric oxide synthase (NOS) genes: NOS1, NOS2A and NOS3, with susceptibility to MS.
  
  
  METHODS
  A total of 122 MS patients and 118 healthy controls screened for NOS1 (rs2682826, rs41279104), NOS2A (CCTTT)n/(TAAA)n and NOS3 (rs1800783, rs1800779, rs2070744, 27bpVNTR) markers, using TaqMan®SNP Genotyping Assays and fragment analysis were enrolled in this study. QRT-PCR and ELISA were used to analyse the expression of NOS3 mRNA and Nitric Oxide (NO) levels.
  
  
  RESULTS
  Two NOS3 markers were associated with susceptibility to MS and early disease development. The NOS3 rs1800779 G-allele (p = 0.04) and GG-genotype (p = 0.02) showed association with susceptibility to MS. Short NOS2 (CCTTT)n (p = 0.03) and short/long repeat (p = 0.04) genotypes also showed associations with MS. These associations were intensified by sub-division of patients into Kuwaiti Arabs and Persians (p < 0.05). The NOS3-27 bp-VNTR a-allele was associated with early MS disease onset ≤26 years (p = 0.04). The NOS3-27 bp-VNTR a/b-genotype resulted in 23% lower NO production and the NOS3-rs1800779 AA-genotype resulted in lower NOS3 expression. Haplotypes obtained from NOS2A and NOS3 showed increased susceptibility to MS. NOS1 showed no significant association with MS.
  
  
  CONCLUSIONS
  This study provides evidence for the association between selected NOS2 and NOS3 markers and MS susceptibility.
authors.affiliation: Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Kuwait. s.alfadhli@hsc.edu.kw
authors.forename: Suad
authors.initials: S
authors.lastname: AlFadhli
authors.forename: Eiman M A
authors.initials: EM
authors.lastname: Mohammed
authors.forename: Asmahan
authors.initials: A
authors.lastname: Al Shubaili
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019075:Electrophoresis, Capillary; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007730:Kuwait / Q000453:epidemiology; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D009569:Nitric Oxide; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III