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Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations
Author(s) -
Ahn Jem Ma,
Kim Chang Ha,
Um Soon Ho,
Kim Kyung Mee,
Kim Tae Hyung,
Yim Sun Young,
Choi Hyuk Soon,
Kim Eun Sun,
Keum Bora,
Seo Yeon Seok,
Yim Hyung Joon,
Jeen Yoon Tae,
Lee Hong Sik,
Chun Hoon Jai,
Kim Chang Duck,
Ryu Ho Sang
Publication year - 2017
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13618
Subject(s) - gastroenterology , medicine , cirrhosis , hepatic encephalopathy , hepatocellular carcinoma , microsatellite , glutaminase , allele , biology , genetics , gene , glutamate receptor , receptor
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.