Validation of Relationship between Variation in the Promoter Region of Glutaminase Gene and Development of Hepatic Encephalopathy in East Asian

Abstract

Background Glutaminase is considered important in develop-ment of hepatic encephalopathy (HE) because it can trigger hyperammonemia and ammonia-induced astrocyte swelling. In a recent study, microsatellite variations in the promoter region of the glutaminase gene are associated with development of HE in white cirrhotic patients with internal cohort validation. However a few external validation studies have been published. Thus the aim of this study was to validate the relationship between microsatellite variations in promoter region and development of over HE in patients with cirrhosis in East Asian population.

Methods We performed a prospective cohort study of 173 cirrhotic patients who underwent microsatellite study in glutaminase gene without previous overt HE history at baseline. The primary end point was the first episode of overt HE. The microsatellite length was categorized into 3 groups based on its repeated number with cut-off value of 13; 52 (30.1%) patients with short-short allele, 94 (54.3%) with short-long, and 27 (15.6%) with long-long.

Results During a 3.1 ± 0.1 years of follow-up (95% confidence interval, 2.9 – 3.2), overt HE developed in 30 patients (17.3%). 3-year cumulative incidence of over HE was 24.4%. There was no significant difference in baseline characteristics between each of groups according to microsatellite length. Multivariate Cox model revealed that hepatocellular carcinoma history, use of diuretics, alcoholic etiology for cirrhosis, minimal HE, high Child-Turcotte-Pugh (CP) score, and high Model for End-Stage Liver Disease (MELD) score were independently associated with HE development. However microsatellite length was not associated with development of over HE.

Conclusions In Korean population with cirrhosis, microsatellite variations in promoter region of the glutaminase gene are not associated with development of overt HE. Thus further study might be needed to identify another genetic factor related with glutaminase activity in Asian with overt HE.