title: Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behçet's disease.
abstract: OBJECTIVE
  Behçet's disease (BD) is a systemic inflammatory vasculitis of young adults with unknown aetiology, characterised by endothelial dysfunction and occlusion in both deep venous and retinal circulation. Ocular involvement occurs in 70% of cases and is characterised by periphlebitis, periarteritis, vascular occlusion, and thrombosis leading to blindness despite vigorous treatment. Endothelin-1 (ET-1) is a vasoconstricting peptide while nitric oxide (NO) is a relaxing molecule and both are released by endothelium for blood flow regulation. Homocysteinaemia is a newly defined term connected to the increased risk of atherothrombotic and atherosclerotic systemic and retinal vascular occlusive diseases, and its role in the course of BD has not been previously described. The authors aimed to detect serum total homocysteine (tHcy), ET-1, and NO in BD and to assess if tHcy, ET-1, and NO are associated with ocular BD or disease activity.
  
  
  METHODS
  43 consecutive patients with ocular (n = 27) or non-ocular (n = 16) BD (36.95 (SD 9.80) years, 22 male, 21 female) satisfying international criteria, and 25 age and sex matched healthy control subjects (37.88 (8.73) years, 13 male, 12 female) without a history of systemic or retinal venous thrombosis were included in this study. Patients were examined by two ophthalmologists with an interest in BD. Serum tHcy, ET-1, and NO concentrations were measured in both groups. Hyperhomocysteinaemia was defined as a tHcy level above the 95th percentile in the control group. Patients were divided into active and inactive period by acute phase reactants including alpha(1) antitrypsin, alpha(2) macroglobulin, erythrocyte sedimentation rate, and neutrophil count.
  
  
  RESULTS
  The overall mean serum tHcy, ET-1, and NO levels were significantly higher in patients with BD than in control subjects (tHcy = 15.83 (4.44) v 7.96 (2.66) ng/ml, p <0.001; ET-1 = 17.47 (4.33) v 5.74 (2.34) micromol/ml, p <0.001; NO = 37.60 (10.31) v 27.08 (7.76) micromol/l, p <0.001). Serum tHcy, ET-1, and NO levels were significantly higher in active patients than in inactive patients and control subjects. In addition, among patients with ocular BD, the mean tHcy levels were significantly increased and correlated with ET-1 and NO levels when compared with non-ocular disease and control subjects. All acute phase reactant levels were significantly higher in active period than in inactive stage and controls.
  
  
  CONCLUSIONS
  Elevated tHcy may be responsible for the endothelial damage in BD and may be an additional risk factor for the development of retinal vascular occlusive disease, contributing to the poor visual outcome in these patients. Assessment of tHcy may be important in the investigation and management of patients with BD, especially with ocular disease.
authors.affiliation: Inonu University Medical Faculty, Turgut Ozal Medical Centre, Research Hospital, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Er
authors.forename: C
authors.initials: C
authors.lastname: Evereklioglu
authors.forename: T
authors.initials: T
authors.lastname: Cumurcu
authors.forename: Y
authors.initials: Y
authors.lastname: Türköz
authors.forename: E
authors.initials: E
authors.lastname: Ozerol
authors.forename: K
authors.initials: K
authors.lastname: Sahin
authors.forename: S
authors.initials: S
authors.lastname: Doganay
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000293:Adolescent; D000328:Adult; D001528:Behcet Syndrome / Q000097:blood / Q000150:complications*; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000209:etiology*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000097:blood; D012164:Retinal Diseases / Q000097:blood / Q000209:etiology*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D019332:Endothelin-1; D006710:Homocysteine; D009569:Nitric Oxide