| Autor: |
Vasavda, Nisha, Menzel, Stephan, Kondaveeti, Sheila, Maytham, Emma, Awogbade, Moji, Bannister, Sybil, Cunningham, Juliette, Eichholz, Andrew, Daniel, Yvonne, Okpala, Iheanyi, Fulford, Tony, Thein, Swee Lay |
| Předmět: |
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| Zdroj: |
British Journal of Haematology; Jul2007, Vol. 138 Issue 2, p263-270, 8p, 2 Charts, 1 Graph |
| Abstrakt: |
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 α-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA]n and HMOX1 [GT]n promoter polymorphisms and α globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/ β0, 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 α-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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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