The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease.
Br J Haematol
; 138(2): 263-70, 2007 Jul.
Article
in En
| MEDLINE
| ID: mdl-17593033
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 alpha 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 alpha-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.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gallstones
/
Glucuronosyltransferase
/
Alpha-Thalassemia
/
Heme Oxygenase-1
/
Anemia, Sickle Cell
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Br J Haematol
Year:
2007
Document type:
Article
Affiliation country:
United kingdom