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Impact of UGT1A1 gene variants on total bilirubin levels in Gilbert syndrome patients and in healthy subjects

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dc.contributor.authorRodrigues, Carina
dc.contributor.authorVieira, Emília
dc.contributor.authorSantos, Rosário
dc.contributor.authorCarvalho, João de
dc.contributor.authorSantos-Silva, Alice
dc.contributor.authorCosta, Elísio
dc.contributor.authorBronze-da-Rocha, Elsa
dc.date.accessioned2018-11-29T12:49:23Z
dc.date.available2018-11-29T12:49:23Z
dc.date.issued2012
dc.description.abstractThe Gilbert syndrome is a benign form of unconjugated hyperbilirubinemia, mainly associated with alterations in UGT1A1 gene. This work investigated the effect of UGT1A1 variants on total bilirubin levels in Gilbert patients (n = 45) and healthy controls (n = 161). Total bilirubin levels were determined using a colorimetric method; molecular analysis of exons 1–5 and two UGT1A1 promoter regions were performed by direct sequencing and automatic analysis of fragments. Five in silico methods predicted the effect of new identified variants. A significant different allelic distribution, in Gilbert patients and in controls, was found for two promoter polymorphisms. Among patients, 82.2% were homozygous and 17.8% heterozygous for the c.− 41_ − 40dupTA allele; in control group, 9.9% were homozygous and 43.5% heterozygous for this promoter variant, while 46.6% (n = 75) presented the [A(TA)6TAA]. For the T>G transition at c.− 3279 promoter region, in patients, 86.7% were homozygous and 13.3% heterozygous; in control group, 33.5% were homozygous for the wild type allele, 44.1% were heterozygous and 22.4% homozygous for the mutated allele. The two polymorphisms were in Hardy–Weinberg equilibrium in both groups. Sequencing of UGT1A1 coding region identified nine novel variants, five in patients and four in controls. In silico analysis of these amino acids replacements predicted four of them as benign and three as damaging. In conclusion, we demonstrated that total bilirubin levels are mainly determined by the TA duplication in the TATA-box promoter and by the c.− 3279T>G variant. Alterations in the UGT1A1 coding region seem to be associated with increased bilirubin levels, and, therefore, with Gilbert syndrome.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRodrigues, C., Vieira, E., Santos, R., Carvalho, J., Santos-Silva, A., Costa, E., Bronze-da-Rocha, E. (2012). Impact of UGT1A1 gene variants on total bilirubin levels in Gilbert syndrome patients and in healthy subjects. Blood Cells, Molecules, and Diseases, 48(3), 166-172pt_PT
dc.identifier.doi10.1016/j.bcmd.2012.01.004pt_PT
dc.identifier.eissn1096-0961
dc.identifier.issn1079-9796
dc.identifier.urihttp://hdl.handle.net/10400.14/26234
dc.identifier.wosWOS:000301470200003
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationSFRH/BD/42791/2007
dc.subjectUGT1A1 variantspt_PT
dc.subjectBilirubin levelspt_PT
dc.subjectPolymorphism phenotype predictionpt_PT
dc.subjectGilbert syndromept_PT
dc.subjectSNPspt_PT
dc.titleImpact of UGT1A1 gene variants on total bilirubin levels in Gilbert syndrome patients and in healthy subjectspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage172
oaire.citation.issue3
oaire.citation.startPage166
oaire.citation.titleBlood Cells, Molecules and Diseasespt_PT
oaire.citation.volume48
person.familyNameRodrigues
person.familyNameSantos
person.familyNameSantos-Silva
person.familyNameCosta
person.familyNameBronze da Rocha
person.givenNameCarina de Fátima
person.givenNameRosário
person.givenNameAlice
person.givenNameElísio
person.givenNameElsa
person.identifier1368242
person.identifier.ciencia-idC415-C677-0253
person.identifier.ciencia-id5717-2E67-9171
person.identifier.ciencia-id3A11-3945-4DC4
person.identifier.ciencia-idC212-09D7-EC3A
person.identifier.orcid0000-0001-9773-1413
person.identifier.orcid0000-0002-8594-6377
person.identifier.orcid0000-0002-2565-3169
person.identifier.orcid0000-0002-3987-7278
person.identifier.orcid0000-0002-3571-2513
person.identifier.ridK-2326-2013
person.identifier.ridK-2723-2013
person.identifier.scopus-author-id8293273700
person.identifier.scopus-author-id7201375082
person.identifier.scopus-author-id6603836490
person.identifier.scopus-author-id7801393706
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication0765ed2c-3e17-43fc-a629-10d338236863
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relation.isAuthorOfPublication.latestForDiscoveryae6f198f-b200-467a-9f35-bb6988b9225e

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