Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations.
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.
['Ahn|Jem Ma|JM|', 'Kim|Chang Ha|CH|', 'Um|Soon Ho|SH|', 'Kim|Kyung Mee|KM|', 'Kim|Tae Hyung|TH|', 'Yim|Sun Young|SY|', 'Choi|Hyuk Soon|HS|', 'Kim|Eun Sun|ES|', 'Keum|Bora|B|', 'Seo|Yeon Seok|YS|', 'Yim|Hyung Joon|HJ|', 'Jeen|Yoon Tae|YT|', 'Lee|Hong Sik|HS|', 'Chun|Hoon Jai|HJ|', 'Kim|Chang Duck|CD|', 'Ryu|Ho Sang|HS|']
D000368:Aged D000483:Alleles D044466:Asians D005202:Far East D005260:Female D005500:Follow-Up Studies D056726:Genetic Association Studies D005972:Glutaminase D006501:Hepatic Encephalopathy D006801:Humans D015994:Incidence D007668:Kidney D008103:Liver Cirrhosis D008297:Male D018895:Microsatellite Repeats D008875:Middle Aged D011401:Promoter Regions, Genetic D011446:Prospective Studies D020080:Tandem Repeat Sequences
glutaminase hepatic encephalopathy liver cirrhosis ammonia genetic variations