UGT1A1 promoter polymorphism associated with serum bilirubin level in Saudi patients with sickle cell disease
Annals of Saudi Medicine, 2013•annsaudimed.net
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 …
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 …
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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