{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T14:45:19Z","timestamp":1777301119488,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,6,7]],"date-time":"2015-06-07T00:00:00Z","timestamp":1433635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatic encephalopathy (<jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content>) is a serious complication of liver cirrhosis. Recently, a microsatellite in the promoter region of the phosphate\u2010activated glutaminase (<jats:styled-content style=\"fixed-case\"><jats:italic>GLS\u00a0<\/jats:italic><\/jats:styled-content>) gene was associated with the risk of <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content>. The aim of the present study was to investigate, using the critical flicker frequency (<jats:styled-content style=\"fixed-case\">CFF<\/jats:styled-content>) test, whether the described <jats:italic><jats:styled-content style=\"fixed-case\">GLS<\/jats:styled-content><\/jats:italic> variant increases the risk of developing <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content> in patients with cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 158 patients (66% men; mean age 59\u00a0years, range 23\u201386) with liver cirrhosis. Mean model for end\u2010stage liver disease score was 13.8 (range 5\u201335); 48% of patients presented with Child\u2013Pugh score B or C. The presence and severity of <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content> were determined by the <jats:styled-content style=\"fixed-case\">CFF<\/jats:styled-content> test, with frequencies \u226439\u00a0Hz denoting cases. <jats:italic><jats:styled-content style=\"fixed-case\">GLS<\/jats:styled-content><\/jats:italic> variants were genotyped by sequencing the microsatellite in the promoter region and were classified as short, long or short\u2013long forms (depending on the length of the macrosatellite alleles).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 53% of patients had abnormal <jats:styled-content style=\"fixed-case\">CFF<\/jats:styled-content> results (i.e. \u226439\u00a0Hz; range for entire cohort 26\u201357). The <jats:italic><jats:styled-content style=\"fixed-case\">GLS<\/jats:styled-content><\/jats:italic> microsatellite distribution amongst patients was short form (20%), long form (32%) and short\u2013long form (48%) and was consistent with Hardy\u2013Weinberg equilibrium. <jats:styled-content style=\"fixed-case\">CFF<\/jats:styled-content> values differed significantly between groups (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.043). Carriers of the <jats:italic><jats:styled-content style=\"fixed-case\">GLS<\/jats:styled-content><\/jats:italic> long microsatellite had a significantly higher risk of <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content> according to multivariate analyses (odds ratio\u00a03.23, 95%\u00a0confidence interval\u00a01.46\u20137.13, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.004).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CFF<\/jats:styled-content> results were significantly lower amongst carriers of the <jats:italic><jats:styled-content style=\"fixed-case\">GLS<\/jats:styled-content><\/jats:italic> long microsatellite. Our findings support the role of the <jats:italic><jats:styled-content style=\"fixed-case\">GLS<\/jats:styled-content><\/jats:italic> long microsatellite in the development of <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content>; this could be important for identifying susceptible patients and for the prevention of this condition.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12374","type":"journal-article","created":{"date-parts":[[2015,4,16]],"date-time":"2015-04-16T12:55:31Z","timestamp":1429188931000},"page":"313-322","source":"Crossref","is-referenced-by-count":11,"title":["A genetic variant in the promoter of phosphate\u2010activated glutaminase is associated with hepatic encephalopathy"],"prefix":"10.1111","volume":"278","author":[{"given":"L. 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