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

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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

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Glutaminase
Hepatic Encephalopathy
Validation Studies
Microsatellite Repeats
Population
Genetic Promoter Regions
Fibrosis
Alcoholic Liver Cirrhosis
End Stage Liver Disease
Tandem Repeat Sequences
Ammonium Compounds
Proportional Hazards Models
Liver Cirrhosis
Hepatocellular Carcinoma
Cohort Studies
Alleles
Prospective Studies

Keywords

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

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

@article{37d5add6227d4f8fba8fbcff9fc69290,
title = "Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations",
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.",
keywords = "ammonia, genetic variations, glutaminase, hepatic encephalopathy, liver cirrhosis",
author = "Ahn, {Jem Ma} and Kim, {Chang Ha} and Soon-Ho Um and Kim, {Kyung Mee} and Kim, {Tae Hyung} and Yim, {Sun Young} and Choi, {Hyuk Soon} and Eun-Sun Kim and Bora Keum and Seo, {Yeon Seok} and Yim, {Hyung Joon} and Jeen, {Yoon Tae} and Lee, {Hong Sik} and Hoon-Jai Chun and Kim, {Chang Duck} and Ryu, {Ho Sang}",
year = "2017",
month = "4",
day = "1",
doi = "10.1111/jgh.13618",
language = "English",
volume = "32",
pages = "901--907",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
issn = "0815-9319",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations

AU - Ahn, Jem Ma

AU - Kim, Chang Ha

AU - Um, Soon-Ho

AU - Kim, Kyung Mee

AU - Kim, Tae Hyung

AU - Yim, Sun Young

AU - Choi, Hyuk Soon

AU - Kim, Eun-Sun

AU - Keum, Bora

AU - Seo, Yeon Seok

AU - Yim, Hyung Joon

AU - Jeen, Yoon Tae

AU - Lee, Hong Sik

AU - Chun, Hoon-Jai

AU - Kim, Chang Duck

AU - Ryu, Ho Sang

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

KW - ammonia

KW - genetic variations

KW - glutaminase

KW - hepatic encephalopathy

KW - liver cirrhosis

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U2 - 10.1111/jgh.13618

DO - 10.1111/jgh.13618

M3 - Article

VL - 32

SP - 901

EP - 907

JO - Journal of Gastroenterology and Hepatology (Australia)

JF - Journal of Gastroenterology and Hepatology (Australia)

SN - 0815-9319

IS - 4

ER -