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The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients
Present study was aimed to explore the effect of (TA)(n) UGT1A1 gene promoter polymorphism on bilirubin metabolism, bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in Sickle-Cell Anemia (SCA) and beta-Thalasemia major (bTH) in Kuwaiti subjects compared to other popul...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813713/ https://www.ncbi.nlm.nih.gov/pubmed/24204915 http://dx.doi.org/10.1371/journal.pone.0077681 |
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author | AlFadhli, Suad Al-Jafer, Hassan Hadi, Mays Al-Mutairi, Mashael Nizam, Rasheeba |
author_facet | AlFadhli, Suad Al-Jafer, Hassan Hadi, Mays Al-Mutairi, Mashael Nizam, Rasheeba |
author_sort | AlFadhli, Suad |
collection | PubMed |
description | Present study was aimed to explore the effect of (TA)(n) UGT1A1 gene promoter polymorphism on bilirubin metabolism, bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in Sickle-Cell Anemia (SCA) and beta-Thalasemia major (bTH) in Kuwaiti subjects compared to other population. This polymorphism was analyzed and correlated to total bilirubin and cholelithiasis in 270 age, gender, ethnically matched subjects (92 bTH, 116 SCA and 62 Controls) using PCR, dHPLC, fragment analysis and direct sequencing. Four genotypes of UGT1A1 were detected in this study (TA6/6, TA6/7, TA6/8 and TA7/7). (TA)6/8 was found only in four individuals; hence it was not included in the analysis. There was a statistically significant association of genotypes with serum total bilirubin levels in both bTH and SCA groups (p<0.001). Subjects with (TA)7/7 had the highest total serum bilirubin level (178.7±3.5 µmole/l). A significant association was observed between allele (TA)7 and cholelithiasis development (p = 0.0001). The 40%, 67.5% and 100% of SCA with (TA)6/6, (TA)6/7 and (TA)7/7 respectively developed cholelithiasis and were subsequently cholecystectomized. Our results confirm UGT1A1 (TA)7 allele as one of the factors accounting for the hyperbilirubinemia and cholelithiasis observed in SCA and bTH. |
format | Online Article Text |
id | pubmed-3813713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38137132013-11-07 The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients AlFadhli, Suad Al-Jafer, Hassan Hadi, Mays Al-Mutairi, Mashael Nizam, Rasheeba PLoS One Research Article Present study was aimed to explore the effect of (TA)(n) UGT1A1 gene promoter polymorphism on bilirubin metabolism, bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in Sickle-Cell Anemia (SCA) and beta-Thalasemia major (bTH) in Kuwaiti subjects compared to other population. This polymorphism was analyzed and correlated to total bilirubin and cholelithiasis in 270 age, gender, ethnically matched subjects (92 bTH, 116 SCA and 62 Controls) using PCR, dHPLC, fragment analysis and direct sequencing. Four genotypes of UGT1A1 were detected in this study (TA6/6, TA6/7, TA6/8 and TA7/7). (TA)6/8 was found only in four individuals; hence it was not included in the analysis. There was a statistically significant association of genotypes with serum total bilirubin levels in both bTH and SCA groups (p<0.001). Subjects with (TA)7/7 had the highest total serum bilirubin level (178.7±3.5 µmole/l). A significant association was observed between allele (TA)7 and cholelithiasis development (p = 0.0001). The 40%, 67.5% and 100% of SCA with (TA)6/6, (TA)6/7 and (TA)7/7 respectively developed cholelithiasis and were subsequently cholecystectomized. Our results confirm UGT1A1 (TA)7 allele as one of the factors accounting for the hyperbilirubinemia and cholelithiasis observed in SCA and bTH. Public Library of Science 2013-10-30 /pmc/articles/PMC3813713/ /pubmed/24204915 http://dx.doi.org/10.1371/journal.pone.0077681 Text en © 2013 AlFadhli et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article AlFadhli, Suad Al-Jafer, Hassan Hadi, Mays Al-Mutairi, Mashael Nizam, Rasheeba The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients |
title | The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients |
title_full | The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients |
title_fullStr | The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients |
title_full_unstemmed | The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients |
title_short | The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients |
title_sort | effect of ugt1a1 promoter polymorphism in the development of hyperbilirubinemia and cholelithiasis in hemoglobinopathy patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813713/ https://www.ncbi.nlm.nih.gov/pubmed/24204915 http://dx.doi.org/10.1371/journal.pone.0077681 |
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