title: Functional variants of eNOS and iNOS genes have no relationship to the portal hypertension in patients with liver cirrhosis.
abstract: OBJECTIVE
  Nitric oxide is an important vasoactive mediator. Changes in NO production, caused by functional variants of both endothelial and inducible NO synthase (eNOS, iNOS), might play a role in portal hypertension. The aim was to study the significance of functional eNOS and iNOS gene variants in cirrhotic patients and their interrelationship to both inflammatory and endothelial activation parameters.
  
  
  METHODS
  One hundred and thirty-two patients with liver cirrhosis (age 36-72 years) and 101 controls were examined for functional variants of eNOS (E298D, 27bpintr4, 786T/C) and iNOS (R221W, S608L) genes. Inflammatory (IL6, IL8, IL10) and vasoactive (sVCAM-1, E-selectin) cytokines were measured using ELISA kits.
  
  
  RESULTS
  The frequency of E298D (GG 12%, GT 41%, TT 47%), 28bpintr4 (AA 6%, AB 28%, BB 66%), 786T/C genotypes (CC 17%, CT 45%, TT 38%), as well as R221W (CC 93%, CT 7%, TT 0%), and S608L (CC 65%, CT 32%, TT 3%) genotypes in cirrhotic patients did not differ from the controls (p > 0.05 for all comparisons). No relationship was found between the frequency of these genotypes and the severity of portal hypertension, or either inflammatory or vasoactive cytokines. A positive correlation was found between hepatic venous pressure gradient and cytokine concentration: sVCAM-1, IL6, IL8, IL10.
  
  
  CONCLUSIONS
  Examined eNOS and iNOS variants have no relationship to pathogenesis of liver cirrhosis. Severity of portal hypertension was associated with the changes in endothelial activation.
authors: Charles University in Prague, 1st Faculty of Medicine, 4th Department of Internal Medicine, U Nemocnice 2, Prague 2, Czech Republic.
authors: Jaromir
authors: J
authors: Petrtyl
authors: Karel
authors: K
authors: Dvorak
authors: Marie
authors: M
authors: Jachymova
authors: Libor
authors: L
authors: Vitek
authors: Martin
authors: M
authors: Lenicek
authors: Petr
authors: P
authors: Urbanek
authors: Ales
authors: A
authors: Linhart
authors: Pavel
authors: P
authors: Jansa
authors: Radan
authors: R
authors: Bruha
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology / Q000235:genetics*; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D017931:DNA Primers; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III