Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations

Jem Ma Ahn, Chang Ha Kim, Soon-Ho Um, Kyung Mee Kim, Tae Hyung Kim, Sun Young Yim, Hyuk Soon Choi, Eun-Sun Kim, Bora Keum, Yeon Seok Seo, Hyung Joon Yim, Yoon Tae Jeen, Hong Sik Lee, Hoon-Jai Chun, Chang Duck Kim, Ho Sang Ryu

Research output: Contribution to journalArticle

Abstract

Background and Aim: In a recent study, microsatellite variations (GCA tandem repeats) in the promoter region of the (kidney-type) glutaminase gene were associated with the development of hepatic encephalopathy (HE) in Spanish patients with cirrhosis. The objective of this study was to validate the relation between microsatellite variations in the glutaminase promoter region and the development of overt HE in Korean patients with liver cirrhosis. Methods: We performed a prospective cohort study of 154 cirrhotic patients who underwent a glutaminase microsatellite study without previous overt HE history at baseline. The primary end point was the first episode of overt HE. The microsatellite length was categorized into three groups based on its repeated number, with a cutoff value of 14; 65 (42.2%), 70 (45.5%), and 19 (12.3%) patients had the short-short, short-long, and long-long alleles, respectively. Results: Over a median 3.5 years of follow-up (range = 0.1–4.4), overt HE developed in 28 patients (18.2%). The 3-year cumulative incidence of overt HE was 18.4%. Multivariate Cox model indicated that past hepatocellular carcinoma history, alcoholic etiology for cirrhosis, higher Model for End-Stage Liver Disease scores and their deterioration, and serum ammonium levels were independently associated with HE development. However, microsatellite length was not associated with the development of overt HE. Conclusions: In Korean patients with cirrhosis, microsatellite variations in the glutaminase promoter region were not associated with development of overt HE. Thus, additional studies are needed to identify other genetic factors related to glutaminase activity in Asians with overt HE.

Original languageEnglish
Pages (from-to)901-907
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume32
Issue number4
DOIs
Publication statusPublished - 2017 Apr 1

Keywords

  • ammonia
  • genetic variations
  • glutaminase
  • hepatic encephalopathy
  • liver cirrhosis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Ahn, J. M., Kim, C. H., Um, S-H., Kim, K. M., Kim, T. H., Yim, S. Y., Choi, H. S., Kim, E-S., Keum, B., Seo, Y. S., Yim, H. J., Jeen, Y. T., Lee, H. S., Chun, H-J., Kim, C. D., & Ryu, H. S. (2017). Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations. Journal of Gastroenterology and Hepatology (Australia), 32(4), 901-907. https://doi.org/10.1111/jgh.13618