title: Hemorheologic profile in systemic sclerosis: role of NOS3 -786T > C and 894G >T polymorphisms in modulating both the hemorheologic parameters and the susceptibility to the disease.
abstract: OBJECTIVE
  Microvascular disorders are relevant in systemic sclerosis (SSc). Hyperviscosity, due to alterations of blood cells and plasma components, may play a role in the pathogenesis of microcirculatory disorders. An impaired availability of nitric oxide, related to polymorphisms in NOS3, the gene for endothelial cell nitric oxide synthase, might influence erythrocyte deformability. We undertook this study to investigate the hemorheologic profile in SSc and the role of NOS3 polymorphisms in modulating the hemorheologic status of SSc patients.
  
  
  METHODS
  We studied 113 consecutive SSc patients (75 with limited cutaneous SSc [lcSSc] and 38 with diffuse cutaneous SSc [dcSSc]) and 113 healthy controls. The hemorheologic profile was obtained by assessing whole blood viscosity (WBV; at shear rates of 0.512 and 94.5 seconds(-1)), plasma viscosity (PLV; at a shear rate of 94.5 seconds(-1)), and erythrocyte deformability index (DI). We determined NOS3 polymorphisms by molecular analysis.
  
  
  RESULTS
  A marked alteration of hemorheologic parameters was found both in patients with lcSSc and in those with dcSSc compared with controls (P < 0.0001). In multivariate analysis, rheologic variables were significantly associated with the disease (for WBV at a shear rate of 94.5 seconds(-1), odds ratio [OR] 5.4, 95% confidence interval [95% CI] 1.4-19.9, P = 0.01; for PLV, OR 2.8, 95% CI 1.2-6.5, P = 0.01; for DI, OR 3.9, 95% CI 1.4-10.8, P = 0.007), and NOS3 -786C and 894T alleles significantly affected the DI (for -786C allele, OR 2.3, 95% CI 1.01-5.4, P = 0.04; for 894T allele, OR 2.2, 95% CI 1.01-4.8, P = 0.04). The simultaneous presence of the -786C and 894T alleles represented a susceptibility factor for SSc (OR 2.8, 95% CI 1.4-5.7, P = 0.004).
  
  
  CONCLUSIONS
  Our findings document an altered rheologic profile in SSc and demonstrate a relationship between this alteration and NOS3 polymorphisms, thus shedding light on a potential novel mechanism influencing the microcirculation in this disease.
authors.affiliation: Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. cinziafatini@hotmail.com
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fatini
authors.forename: Lucia
authors.initials: L
authors.lastname: Mannini
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.forename: Veronica
authors.initials: V
authors.lastname: Rogai
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Conforti
authors.forename: Marina
authors.initials: M
authors.lastname: Cinelli
authors.forename: Alberto Moggi
authors.initials: AM
authors.lastname: Pignone
authors.forename: Paola
authors.initials: P
authors.lastname: Bolli
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Marco Matucci
authors.initials: MM
authors.lastname: Cerinic
mesh_terms: D000368:Aged; D000483:Alleles; D001775:Blood Circulation / Q000235:genetics / Q000502:physiology*; D001783:Blood Flow Velocity / Q000235:genetics / Q000502:physiology; D001809:Blood Viscosity / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000032:analysis; D004907:Erythrocyte Deformability / Q000235:genetics / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D008875:Middle Aged; D015999:Multivariate Analysis; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D004247:DNA; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III