title: UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients: Outcomes from a case-control study.
abstract: Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A1*28 (UGT1A1*28). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions' to the liver disease scenario. Our aim was to assess UGT1A1 genotypes' frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case-control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)-polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients. Genotypes and alleles frequencies were similar in case (n = 585; P = 0.101) and control groups (n = 313; P = 0.795). Total bilirubin increase was noticed according to thymine-adenine repeats in genotypes (P < 0.001), and the TB greater than 1 mg/dL group had more UGT1A1*28 subjects than in the group with TB values <1 mg/dL (18.3 vs 5.3; P < 0.001). Bilirubin levels are linked to the studied polymorphisms, and this is the first time that these findings are reported in a chronic liver disease sample. Among patients with increased TB levels, the frequency of UGT1A1*28 is higher than those with normal TB. Personalized care should be considered to GS, regarding either abnormal bilirubin levels or drug metabolism.
authors.affiliation: Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Marcelo Moreira Tavares
authors.initials: MMT
authors.lastname: de Souza
authors.forename: Victor Van
authors.initials: VV
authors.lastname: Vaisberg
authors.forename: Rodrigo Martins
authors.initials: RM
authors.lastname: Abreu
authors.forename: Aline Siqueira
authors.initials: AS
authors.lastname: Ferreira
authors.forename: Camila
authors.initials: C
authors.lastname: daSilvaFerreira
authors.forename: Paulo Dominguez
authors.initials: PD
authors.lastname: Nasser
authors.forename: Helena Scavone
authors.initials: HS
authors.lastname: Paschoale
authors.forename: Flair José
authors.initials: FJ
authors.lastname: Carrilho
authors.forename: Suzane Kioko
authors.initials: SK
authors.lastname: Ono
mesh_terms: D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005878:Gilbert Disease / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme