INOS and eNOS Genotypes and Expression in Hepatitis E-Related Acute Liver Failure

Abstract

Introduction: The study was aimed to determine the role of iNOS and eNOS genotypes in their expression in hepatitis E virus (HEV)-related acute liver failure (ALF). Methods: The study group included 294 acute viral hepatitis (AVH), 82 ALF and 331 healthy controls. Expression study of iNOS and eNOS was done using commercially available ELISA kits. Polymorphism of iNOS C150T and eNOS G894T was studied using the PCR-RFLP method. Determination of the iNOS and eNOS gene mutations was done using the TSP509I restriction enzyme for iNOS and Ban II restriction enzyme for eNOS. Pearson correlation analysis was done to observe the correlations between iNOS and eNOS with the parameters for the severity of disease (viral load, prothrombin time, total bilirubin, SGOT, SGPT, and ALP). Results: On comparing the iNOS levels corresponding to its genotype in the study group, we observed that the subjects carrying the CT+TT mutant genotype had significantly higher levels of iNOS compared to the wild type CC genotype (24.9± 6.9 vs.16.74±5.1; p<0.001, 62.16±1.6 vs. 54.26 ±6.1, p<0.001, and 10.57±5.15 vs.7.36±2.5, p<0.001). Similarly, on comparing the eNOS levels corresponding to its genotype in the study groups, we observed that the subjects carrying the GT+TT mutant genotype had significantly higher levels of eNOS compared to the wild type GG genotype (27.3± 7.2 vs.21.45±5.1, p<0.001, 64.1±1.8 vs. 58.5 ±2.8, p<0.001 and 17.9±4.8 vs.14.6±4.3, p<0.001). Significant positive correlation was observed between the iNOS and eNOS levels in the HEV-infected patient (AVH and ALF) and the severity of disease parameters i.e viral load, prothrombin time, total bilirubin, direct bilirubin, SGOT, and SGPT levels. Conclusion: iNOS and eNOS mutant genotype significantly increases the levels of iNOS and eNOS, as compared to wild type. The iNOS C150T polymorphism and the eNOS G894T polymorphism and high levels of iNOS and eNOS are associated with an increased risk of HEV-related acute hepatitis and liver failure.