title: Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jem Ma
authors.initials: JM
authors.lastname: Ahn
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Chang Ha
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Kyung Mee
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yim
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyuk Soon
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Keum
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yim
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Yoon Tae
authors.initials: YT
authors.lastname: Jeen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hong Sik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hoon Jai
authors.initials: HJ
authors.lastname: Chun
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Chang Duck
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Ho Sang
authors.initials: HS
authors.lastname: Ryu
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People; D005202:Asia, Eastern / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D005972:Glutaminase / Q000235:genetics*; D006501:Hepatic Encephalopathy / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000201:enzymology*; D008103:Liver Cirrhosis / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D005972:Glutaminase
keywords: ammonia; genetic variations; glutaminase; hepatic encephalopathy; liver cirrhosis