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

Carlo Selmi, Massimo Zuin, Maria Luisa Biondi, Pietro Invernizzi, Pier Maria Battezzati, Mara Bernini, Francesca Meda, M. Eric Gershwin, Mauro Podda

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1150-1155
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume18
Issue number10
DOIs
StatePublished - 2003

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Biliary Liver Cirrhosis
Nitric Oxide Synthase Type III
Genotype
Disease Progression
Experimental Liver Cirrhosis
Cholestasis
Disease Susceptibility
Portal Hypertension
Genetic Polymorphisms
Fluorescent Dyes
Liver Transplantation
Healthy Volunteers
Nitric Oxide
Theoretical Models
Alleles
Control Groups
Liver
DNA
Wounds and Injuries

Keywords

  • Endothelial nitric oxide synthase
  • Genetics
  • Primary biliary cirrhosis
  • Progression

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Genetic variants of endothelial nitric oxide synthase in patients with primary biliary cirrhosis : Association with disease severity. / Selmi, Carlo; Zuin, Massimo; Biondi, Maria Luisa; Invernizzi, Pietro; Battezzati, Pier Maria; Bernini, Mara; Meda, Francesca; Gershwin, M. Eric; Podda, Mauro.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 18, No. 10, 2003, p. 1150-1155.

Research output: Contribution to journalArticle

Selmi, Carlo ; Zuin, Massimo ; Biondi, Maria Luisa ; Invernizzi, Pietro ; Battezzati, Pier Maria ; Bernini, Mara ; Meda, Francesca ; Gershwin, M. Eric ; Podda, Mauro. / Genetic variants of endothelial nitric oxide synthase in patients with primary biliary cirrhosis : Association with disease severity. In: Journal of Gastroenterology and Hepatology (Australia). 2003 ; Vol. 18, No. 10. pp. 1150-1155.
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T1 - Genetic variants of endothelial nitric oxide synthase in patients with primary biliary cirrhosis

T2 - Association with disease severity

AU - Selmi, Carlo

AU - Zuin, Massimo

AU - Biondi, Maria Luisa

AU - Invernizzi, Pietro

AU - Battezzati, Pier Maria

AU - Bernini, Mara

AU - Meda, Francesca

AU - Gershwin, M. Eric

AU - Podda, Mauro

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

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