Genetic variants of endothelial nitric oxide synthase in patients with primary biliary cirrhosis: association with disease severity

BACKGROUND AND AIMS: 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.