Effects of SNPs in HE-relevant genes for the development of hepatic encephalopathy

Background Hepatic encephalopathy (HE) is a frequent complication in acute and chronic liver failure and a negative prognostic factor for mortality in patients with liver cirrhosis. Currently, HE is seen as the clinical manifestation of a low grade cerebral edema and cerebral oxidative stress which disturbs oscillatory networks and synaptic plasticity in brain.

Aims and Methods To identify genetic risk factors for the development of a hepatic encephalopathy a Next Generation Sequencing (NGS) chip was developed, representing the whole coding region including selected promoter regions in 7 genes that potentially play a role in the pathogenesis of HE.

DNA samples were collected from 48 patients with liver cirrhosis and at least one episode of hepatic encephalopathy, 34 patients with diagnosed liver cirrhosis who never had an episode of HE so far and 30 controls, with no known liver disease. In addition DNA samples were collected from frozen brain tissue from donors of the body donor program of the University of Düsseldorf (9 patients with cirrhosis and HE, 7 controls without liver cirrhosis).

Results 55 SNPs could be identified which were not specific for patients with liver cirrhosis and hepatic encephalopathy and were also found in controls and patients with liver cirrhosis without an episode of HE. For the glutamate transporter 1 (GLT-1) we could identify two SNPs (rs752949, rs1042113) that have a lower allele frequency in patients with liver cirrhosis and HE than in the control group of patients with no liver cirrhosis or our additional control group from the database gnomAD without reaching statistically significance yet. This was also the case for the SNPs rs3027958 and rs1042113 of SCL1A5.

Of particular interest we could identify 2 SNPs of SLC1A5 (rs1060043 and rs2070246) with a statistically significant increase of their allele frequency in patients with liver cirrhosis and HE compared to the group of patients with liver cirrhosis and no known episode of HE (18 % vs. 3 % and 27 % vs. 11 %).

Discussion Our study suggests that SNPs may play a role for the pathogenesis of HE. However, further patients need to be included in this study to validate the present findings and further research is needed to identify consequences of the individual SNPs for the respective protein function.

Supported by DFG through SFB 974.

Publication History

Article published online:
04 January 2021