Endothelial nitric oxide synthase gene polymorphism and its association with the risk of esophageal varices in patients with liver cirrhosis

Abstract EN

Background : Esophageal varices (EV) is a frequent complication among patients with liver cirrhosis.

Nitric oxide (NO) and other vasoactive molecules regulate the vascular tone in both the liver microcirculation and the systemic and splanchnic circulation.

Endothelial nitric oxide synthase (eNOS) gene -which encodes NO- is polymorphic, and this polymorphism has been associated with several cardiovascular diseases.

Objective : The aim of this work was to find a relationship between eNOS gene polymorphism and serum nitrite/nitrate levels, degree of portal hypertension, development of EV, and risk of EV bleeding among cirrhotic patients.

Methods : This study was carried out on 75 patients with liver cirrhosis and 50 healthy control subjects.

All subjects were subjected to measuring serum nitrite / nitrate levels as an index of NO synthesis, and genotyping by polymerase chain reaction for the eNOS 4 / 5 (intron 4) polymorphism.

Ultrasound abdomen and Doppler study of the portal venous system and upper gastrointestinal endoscopy were done for all cirrhotic patients.

Results : Serum nitrite / nitrate levels were found to be significantly higher in cirrhotic patients with EV than in cirrhotic patients without EV.

Higher serum nitrite / nitrate levels were found to be associated with larger sized EV and correlated with risk of EV bleeding.

The prevalence of eNOS genotype 5 / 5 was significantly higher in cirrhotic patients with than without EV.

Portal vein congestion index (PCI) was found to be higher in cirrhotic patients of eNOS genotype 5 / 5.

eNOS genotype 5 / 5 was found to be associated with a higher serum nitrite / nitrate levels in cirrhotic patients and healthy control subjects.

Genotype 5 / 5 was found to be associated with larger sized EV, advanced EV red spot score, and advanced grade of gastric varices.

Conclusion : Our results support that we can identify cirrhotic patients at higher risk of developing EV through identification of their eNOS genotype