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UGT1A1 promoter polymorphism associated with serum bilirubin level in Saudi patients with sickle cell disease

BACKGROUND AND OBJECTIVES: Polymorphism in (TA)n of the UGT1A1 promoter influences bilirubin level and risk of gallstones in patients with sickle cell disease (SCD) of African descent. Modifiers of bilirubin level and gallstones in Saudi patients with SCD are not known. DESIGN AND SETTINGS: Patients...

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Detalles Bibliográficos
Autores principales: Hamad, Zainab, Aljedai, Abdullah, Halwani, Rabih, AlSultan, Abdulrahman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: King Faisal Specialist Hospital and Research Centre 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078505/
https://www.ncbi.nlm.nih.gov/pubmed/24060717
http://dx.doi.org/10.5144/0256-4947.2013.372
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author Hamad, Zainab
Aljedai, Abdullah
Halwani, Rabih
AlSultan, Abdulrahman
author_facet Hamad, Zainab
Aljedai, Abdullah
Halwani, Rabih
AlSultan, Abdulrahman
author_sort Hamad, Zainab
collection PubMed
description BACKGROUND AND OBJECTIVES: Polymorphism in (TA)n of the UGT1A1 promoter influences bilirubin level and risk of gallstones in patients with sickle cell disease (SCD) of African descent. Modifiers of bilirubin level and gallstones in Saudi patients with SCD are not known. DESIGN AND SETTINGS: Patients with SCD presenting to participating institutions between July 2009 and July 2012 were enrolled in our study. METHODS: A total of 223 SCD patients were enrolled. Laboratory workup at steady state included complete blood count, reticulocytes, serum bilirubin, lactate dehydrogenase (LDH), G6PD level, and hemoglobin (Hb) electrophoresis. The (TA)n UGT1A1 promoter polymorphism and presence of α-thalassemia were also determined. RESULTS: TA6/6 in the UGT1A1 promoter was identified in 189 patients (84.7%), TA7/7 in 26 (11.7%), TA5/5 in 6 (2.7%), and TA5/6 in 2 (0.9%). Increased (TA)n of the UGT1A1 promoter (P<.0001), male gender (P=.02), higher LDH (P=.001), and lower Hb level (P=.009) were associated with higher bilirubin level, while the co-inheritance of α-thalassemia (P=.003) was linked with lower bilirubin level. UGT1A1 (TA)n (P<.0001) and Hb level (P=.005) remained significant on multivariate analysis. Gallstones were more frequent in patients with TA7/7 (72%) compared to patients with TA6/6 (57%) and TA5/5 or 5/6 (37%); however, this difference was not statistically significance (P=.18). Older age (P=.0001) and absence of α-thalassemia (P=.03) were associated with higher risk of gallstones. CONCLUSION: (TA)n in the UGT1A1 promoter and intensity of hemolysis modify steady-state serum bilirubin level in SCD. Co-inheritance of α-thalassemia reduces the risk of gallstones in Saudi patients with SCD.
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spelling pubmed-60785052018-09-21 UGT1A1 promoter polymorphism associated with serum bilirubin level in Saudi patients with sickle cell disease Hamad, Zainab Aljedai, Abdullah Halwani, Rabih AlSultan, Abdulrahman Ann Saudi Med Original Article BACKGROUND AND OBJECTIVES: Polymorphism in (TA)n of the UGT1A1 promoter influences bilirubin level and risk of gallstones in patients with sickle cell disease (SCD) of African descent. Modifiers of bilirubin level and gallstones in Saudi patients with SCD are not known. DESIGN AND SETTINGS: Patients with SCD presenting to participating institutions between July 2009 and July 2012 were enrolled in our study. METHODS: A total of 223 SCD patients were enrolled. Laboratory workup at steady state included complete blood count, reticulocytes, serum bilirubin, lactate dehydrogenase (LDH), G6PD level, and hemoglobin (Hb) electrophoresis. The (TA)n UGT1A1 promoter polymorphism and presence of α-thalassemia were also determined. RESULTS: TA6/6 in the UGT1A1 promoter was identified in 189 patients (84.7%), TA7/7 in 26 (11.7%), TA5/5 in 6 (2.7%), and TA5/6 in 2 (0.9%). Increased (TA)n of the UGT1A1 promoter (P<.0001), male gender (P=.02), higher LDH (P=.001), and lower Hb level (P=.009) were associated with higher bilirubin level, while the co-inheritance of α-thalassemia (P=.003) was linked with lower bilirubin level. UGT1A1 (TA)n (P<.0001) and Hb level (P=.005) remained significant on multivariate analysis. Gallstones were more frequent in patients with TA7/7 (72%) compared to patients with TA6/6 (57%) and TA5/5 or 5/6 (37%); however, this difference was not statistically significance (P=.18). Older age (P=.0001) and absence of α-thalassemia (P=.03) were associated with higher risk of gallstones. CONCLUSION: (TA)n in the UGT1A1 promoter and intensity of hemolysis modify steady-state serum bilirubin level in SCD. Co-inheritance of α-thalassemia reduces the risk of gallstones in Saudi patients with SCD. King Faisal Specialist Hospital and Research Centre 2013 /pmc/articles/PMC6078505/ /pubmed/24060717 http://dx.doi.org/10.5144/0256-4947.2013.372 Text en Copyright © 2013, Annals of Saudi Medicine This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Hamad, Zainab
Aljedai, Abdullah
Halwani, Rabih
AlSultan, Abdulrahman
UGT1A1 promoter polymorphism associated with serum bilirubin level in Saudi patients with sickle cell disease
title UGT1A1 promoter polymorphism associated with serum bilirubin level in Saudi patients with sickle cell disease
title_full UGT1A1 promoter polymorphism associated with serum bilirubin level in Saudi patients with sickle cell disease
title_fullStr UGT1A1 promoter polymorphism associated with serum bilirubin level in Saudi patients with sickle cell disease
title_full_unstemmed UGT1A1 promoter polymorphism associated with serum bilirubin level in Saudi patients with sickle cell disease
title_short UGT1A1 promoter polymorphism associated with serum bilirubin level in Saudi patients with sickle cell disease
title_sort ugt1a1 promoter polymorphism associated with serum bilirubin level in saudi patients with sickle cell disease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078505/
https://www.ncbi.nlm.nih.gov/pubmed/24060717
http://dx.doi.org/10.5144/0256-4947.2013.372
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