{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T18:53:59Z","timestamp":1776106439777,"version":"3.50.1"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Gilbert Syndrome (GS) is a common hereditary disorder characterized by intermittent jaundice. The pathogenesis is unconjugated hyperbilirubinemia due to reduced hepatic UDP-glucuronosyltransferase 1A1 (UGT1A1) activity. Its genetic basis relies on c.-3279T\u2009&gt;\u2009G polymorphism (UGT1A1*60), which reduces gene transcription by approximately 40%, and is highly prevalent in Asian populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aimed to profile the genetic, biochemical, and clinical characteristics of individuals with clinical features of GS in Nepal and examine correlations between UGT1A1 genotypes and hematological parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study utilized a prospective descriptive design supplemented by a retrospective review of medical records, including 75 patients with isolated unconjugated hyperbilirubinemia. Prospective recruitment and data collection were conducted from July 18, 2025, to November 30, 2025. Medical records from outside facilities were accessed for research purposes from July 18, 2025, to November 30, 2025, covering records dating back to January 1, 2021. Patients underwent ARMS-PCR genetic testing for the UGT1A1 c.-3279T\u2009&gt;\u2009G variant.Patients with hemolysis or hepatobiliary disease were excluded. Genetic confirmation of GS was based on the presence of the G allele.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mean age of cohort was 28.9\u2009\u00b1\u200910.4 years (range: 14\u201355), with a male predominance (69.3%). Genotype distribution revealed 66.7% homozygous mutant (G\/G), 29.3% heterozygous (G\/T), and 4% wild-type (T\/T), yielding a G allele frequency of 81.3%. Mean bilirubin levels showed a genotype-phenotype correlation: G\/G (4.3\u2009\u00b1\u20091.1 mg\/dL), G\/T (3.2\u2009\u00b1\u20090.9 mg\/dL), and T\/T (2.4\u2009\u00b1\u20090.3 mg\/dL). Hematological parameters were within normal reference ranges across all genotypes, confirming the non-hemolytic nature of the condition. No hepatosplenomegaly was detected on ultrasonography.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates an exceptionally high prevalence of the UGT1A1*60 G allele among individuals with clinical features of GS in Nepal. These findings reaffirm the benign, non-hemolytic character of GS and underscore the diagnostic and pharmacogenetic utility of UGT1A1 genotyping in the Nepali population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0347128","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T17:29:29Z","timestamp":1776101369000},"page":"e0347128","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic, clinical, and biochemical profiling of Gilbert syndrome in a Nepali cohort: High prevalence of the UGT1A1 c.-3279T&gt;G polymorphism and correlation with hematological parameters"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7992-7663","authenticated-orcid":true,"given":"Pragya 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A"},{"issue":"1","key":"pone.0347128.ref002","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0168-8278(02)00359-8","article-title":"Inherited disorders of bilirubin metabolism","volume":"38","author":"PJ Bosma","year":"2003","journal-title":"J Hepatol"},{"issue":"5","key":"pone.0347128.ref003","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.bpg.2010.07.007","article-title":"Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome)","volume":"24","author":"CP Strassburg","year":"2010","journal-title":"Best Pract Res Clin Gastroenterol"},{"issue":"18","key":"pone.0347128.ref004","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1056\/NEJM199511023331802","article-title":"The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert\u2019s syndrome","volume":"333","author":"PJ Bosma","year":"1995","journal-title":"N Engl J 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Pediatr"},{"issue":"8","key":"pone.0347128.ref008","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1200\/JCO.2004.07.173","article-title":"Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan","volume":"22","author":"F Innocenti","year":"2004","journal-title":"J Clin Oncol"},{"issue":"1","key":"pone.0347128.ref009","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3126\/jnps.v35i1.10620","article-title":"Differentiating Gilbert syndrome from Crigler Najjar syndrome type 2 by phenobarbitone test","volume":"35","author":"R Sinha","year":"2015","journal-title":"J Nepal Paedtr Soc"},{"issue":"3","key":"pone.0347128.ref010","first-page":"187","article-title":"A case report of Gilbert Syndrome","volume":"1","author":"SR Manandhar","year":"2003","journal-title":"Kathmandu Univ Med J"},{"issue":"2","key":"pone.0347128.ref011","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/10408363.2018.1428526","article-title":"Diagnostic criteria and contributors to Gilbert's syndrome","volume":"55","author":"KH Wagner","year":"2018","journal-title":"Crit Rev Clin Lab Sci"},{"issue":"6","key":"pone.0347128.ref012","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1097\/00008571-200008000-00007","article-title":"Variations of the bilirubin uridine-diphosphoglucuronosyl transferase 1A1 gene in healthy Taiwanese","volume":"10","author":"CS Huang","year":"2000","journal-title":"Pharmacogenetics"},{"issue":"1","key":"pone.0347128.ref013","first-page":"21","article-title":"Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese","volume":"46","author":"K Akaba","year":"1998","journal-title":"Biochem Mol Biol Int"},{"issue":"3","key":"pone.0347128.ref014","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3343\/alm.2020.40.3.281","article-title":"Genetic spectrum of UGT1A1 in Korean patients with unconjugated Hyperbilirubinemia","volume":"40","author":"JJ Kim","year":"2020","journal-title":"Ann Lab Med"},{"issue":"1","key":"pone.0347128.ref015","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/S1079-9796(03)00071-8","article-title":"The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications","volume":"31","author":"A Premawardhena","year":"2003","journal-title":"Blood Cells Mol Dis"},{"issue":"11","key":"pone.0347128.ref016","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1373\/clinchem.2005.055681","article-title":"The polymorphism c.-3279T>G in the phenobarbital-responsive enhancer module of the bilirubin UDP-glucuronosyltransferase gene is associated with 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irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphism","volume":"65","author":"L Iyer","year":"1999","journal-title":"Clin Pharmacol Ther"},{"issue":"11","key":"pone.0347128.ref020","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1124\/dmd.105.005447","article-title":"In vitro inhibition of UDP glucuronosyltransferases by atazanavir and other HIV protease inhibitors and the relationship of this property to in vivo bilirubin glucuronidation","volume":"33","author":"D Zhang","year":"2005","journal-title":"Drug Metab Dispos"},{"issue":"7","key":"pone.0347128.ref021","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1111\/liv.15239","article-title":"Disease burden and management of Crigler-Najjar syndrome: Report of a world registry","volume":"42","author":"SJ Aronson","year":"2022","journal-title":"Liver 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