2012
DOI: 10.1002/hep.25561
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Gilbert syndrome redefined: A complex genetic haplotype influences the regulation of glucuronidation

Abstract: Gilbert syndrome (GS) is characterized by intermittent unconjugated hyperbilirubinemia without structural liver damage, affecting about 10% of the white population. In GS the UGT1A1*28 variant reduces bilirubin conjugation by 70% and is associated with irinotecan and protease inhibitor side effects. The aim of this study was to characterize potential in vivo consequences of UGT1A gene variability in GS. Three hundred GS patients (UGT1A1*28 homozygous) and 249 healthy blood donors (HBD) were genotyped for UGT1A… Show more

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Cited by 49 publications
(41 citation statements)
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“…32 Although this was a small study, it raises the possibility of survival bias in case-control studies of alleles influencing bilirubin levels and CVD. Further replication in large cohorts with a young recruitment age, extended followup, careful recording of CVD-related drug prescriptions, and inclusion of variants influencing bilirubin levels in addition to UGT1A1*28 2,33 is required to clarify the relationship between alleles causing hyperbilirubinemia and CVD risk.…”
Section: Discussionmentioning
confidence: 99%
“…32 Although this was a small study, it raises the possibility of survival bias in case-control studies of alleles influencing bilirubin levels and CVD. Further replication in large cohorts with a young recruitment age, extended followup, careful recording of CVD-related drug prescriptions, and inclusion of variants influencing bilirubin levels in addition to UGT1A1*28 2,33 is required to clarify the relationship between alleles causing hyperbilirubinemia and CVD risk.…”
Section: Discussionmentioning
confidence: 99%
“…Due to the phenomenon of linkage disequilibrium, most UGT1A1*28 homozygotes also have deficiencies in other UGT1A isoforms encoded just downstream of UGT1A1 [35]. All UGT1A isoforms are drug metabolising enzymes and a number of pharmacogenetic studies and investigations in patients with Gilbert's syndrome suggest altered glucuronidation capacity toward a range of common agents including 13 aspirin, paracetamol and statins [35][36][37].…”
Section: Discussionmentioning
confidence: 99%
“…All UGT1A isoforms are drug metabolising enzymes and a number of pharmacogenetic studies and investigations in patients with Gilbert's syndrome suggest altered glucuronidation capacity toward a range of common agents including 13 aspirin, paracetamol and statins [35][36][37]. Given the high prevalence of the genetic variation underlying Gilbert's syndrome and the high burden of adverse reactions to these agents, further research into drug response is warranted.…”
Section: Discussionmentioning
confidence: 99%
“…In particular, the common UGT1A1 allele 28 polymorphism (UGT1A1*28), which is necessary, but not sufficient, for the clinical expression of Gilbert's syndrome (8), was more frequent in acromegalics with hepatotoxicity, thus representing, together with male gender, a predictor of LFT abnormalities (7). Other studies pointed out a role of diabetes mellitus, with significant odds ratios (OR) (from 2 to 5) for the association with PEG-V hepatotoxicity (9,10).…”
Section: Introductionmentioning
confidence: 99%