The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease

N Vasavda; S Menzel; S Kondaveeti; E Maytham; M Awogbade; S Bannister; J Cunningham; A Eichholz; Y Daniel; I Okpala; T Fulford; S L Thein

doi:10.1111/j.1365-2141.2007.06643.x

The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease

N Vasavda, S Menzel, S Kondaveeti, E Maytham, M Awogbade, S Bannister, J Cunningham, A Eichholz, Y Daniel, I Okpala, T Fulford, S L Thein

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Abstract

Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and alpha-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA](n) and HMOX1 [GT](n) promoter polymorphisms and a globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/beta(0), 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P <0 0001 and P <0 01, respectively). While HMOX1 genotype had no effect, co-inheritance of a-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD

Original language	English
Pages (from-to)	263 - 270
Number of pages	8
Journal	British Journal of Haematology
Volume	138
Issue number	2
DOIs	https://doi.org/10.1111/j.1365-2141.2007.06643.x
Publication status	Published - Jul 2007

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Vasavda, N., Menzel, S., Kondaveeti, S., Maytham, E., Awogbade, M., Bannister, S., Cunningham, J., Eichholz, A., Daniel, Y., Okpala, I., Fulford, T., & Thein, S. L. (2007). The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease. British Journal of Haematology, 138(2), 263 - 270. https://doi.org/10.1111/j.1365-2141.2007.06643.x

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title = "The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease",

abstract = "Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and alpha-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA](n) and HMOX1 [GT](n) promoter polymorphisms and a globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/beta(0), 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P <0 0001 and P <0 01, respectively). While HMOX1 genotype had no effect, co-inheritance of a-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD",

author = "N Vasavda and S Menzel and S Kondaveeti and E Maytham and M Awogbade and S Bannister and J Cunningham and A Eichholz and Y Daniel and I Okpala and T Fulford and Thein, {S L}",

year = "2007",

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doi = "10.1111/j.1365-2141.2007.06643.x",

language = "English",

volume = "138",

pages = "263 -- 270",

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Vasavda, N, Menzel, S, Kondaveeti, S, Maytham, E, Awogbade, M, Bannister, S, Cunningham, J, Eichholz, A, Daniel, Y, Okpala, I, Fulford, T & Thein, SL 2007, 'The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease', British Journal of Haematology, vol. 138, no. 2, pp. 263 - 270. https://doi.org/10.1111/j.1365-2141.2007.06643.x

TY - JOUR

T1 - The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease

AU - Vasavda, N

AU - Menzel, S

AU - Kondaveeti, S

AU - Maytham, E

AU - Awogbade, M

AU - Bannister, S

AU - Cunningham, J

AU - Eichholz, A

AU - Daniel, Y

AU - Okpala, I

AU - Fulford, T

AU - Thein, S L

PY - 2007/7

Y1 - 2007/7

N2 - Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and alpha-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA](n) and HMOX1 [GT](n) promoter polymorphisms and a globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/beta(0), 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P <0 0001 and P <0 01, respectively). While HMOX1 genotype had no effect, co-inheritance of a-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD

AB - Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and alpha-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA](n) and HMOX1 [GT](n) promoter polymorphisms and a globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/beta(0), 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P <0 0001 and P <0 01, respectively). While HMOX1 genotype had no effect, co-inheritance of a-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD

U2 - 10.1111/j.1365-2141.2007.06643.x

DO - 10.1111/j.1365-2141.2007.06643.x

M3 - Article

SN - 1365-2141

VL - 138

SP - 263

EP - 270

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 2

ER -

The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease

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