title: Genetic variants of endothelial nitric oxide synthase in patients with primary biliary cirrhosis: association with disease severity.
abstract: OBJECTIVE
  Primary biliary cirrhosis (PBC) presents a wide spectrum of clinical manifestations. In experimental models of liver cirrhosis and cholestasis it has been suggested that altered nitric oxide production is involved in liver injury and portal hypertension development. The present study investigated endothelial nitric oxide synthase (eNOS) genetic polymorphisms (894G/T, -786T/C) in patients with PBC and in controls to verify whether disease susceptibility and progression are associated with a particular genotype.
  
  
  METHODS
  Genomic DNA from 109 Italian PBC patients (65 with advanced disease, i.e. liver transplantation or histological stage III-IV) was obtained and polymorphisms determined by fluorescent probe analysis. Healthy subjects (n = 242) were used as a control group.
  
  
  RESULTS
  The allelic frequencies of both polymorphisms did not differ significantly between PBC patients and controls. When the association between genotypes and disease severity was addressed, both the 894T and the -786T alleles were more frequently found in the 22 patients with progressing disease (894T, frequency 0.455 compared with 0.240; P = 0.032; -786T, frequency 0.682 compared with 0.460; P = 0.038). Patients with 894TT presented higher Mayo score values (6.1 +/- 1.2 compared with 5.4 +/- 1.3 in 894G/G patients; P = 0.030) but similar age and disease duration values.
  
  
  CONCLUSIONS
  The authors suggest that genetic variants of eNOS are not associated with susceptibility to PBC, although the genotypes may lead to differences in disease severity and progression.
authors.affiliation: Division of Internal Medicine, Department of Medicine, Surgery and Dentistry, University of Milan, Division of Clinical Chemistry and Microbiology, San Paolo Hospital, Milan, Italy. carlo.selmi@unimi.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Selmi
authors.forename: Massimo
authors.initials: M
authors.lastname: Zuin
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Biondi
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.forename: Pier Maria
authors.initials: PM
authors.lastname: Battezzati
authors.forename: Mara
authors.initials: M
authors.lastname: Bernini
authors.forename: Francesca
authors.initials: F
authors.lastname: Meda
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Mauro
authors.initials: M
authors.lastname: Podda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics*; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D020641:Polymorphism, Single Nucleotide
chemical_list: C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III