The influence of uridine diphosphate glucuronosyl transferase 1A promoter polymorphisms, βS-globin gene haplotype, co-inherited α-thalassemia trait and Hb F on steady-state serum bilirubin levels in sickle cell anemia.

Purpose: Homozygosity for the (AT)7 allele of uridine diphosphate glucuronosyl transferase IA (UGTIAI) gene polymorphism is associated with increased bilirubin levels in sickle cell anemia (SCA). In the present study, in addition to UGTIAI promoter genotype, serum bilirubin level was related to other genetic modifiers - βS-globin gene haplotype, Hb F, co-inherited α-thal trait, age and gender. Methods: The patients were randomly selected from the sickle cell clinic, Medical College of Georgia. UGTIAI promoter polymorphisms were determined using automated sequencing. Other investigations were with standard techniques. Results: There were 67 SCA patients (41 males and 26 females), aged 2-44 yr (mean of 20.6 ± 10.7). Ten (14.9%) patients were homozygous for the (AT)6 UGTIAI allele, 35 (52.2%) were heterozygous for (AT)6 and (AT)7 alleles while 22 (32.8%) were homozygous for (AT)7. Serum bilirubin was significantly higher in the homozygous (AT)7 group (3.7 ± 1.5, 3.8 ± 2.3 and 5.6 ± 2.4 mg/dL, respectively). It was also significantly higher in males than females and in patients aged > 10 yr. There was a significant negative linear correlation (r = -0.304, P = 0.016) of serum bilirubin with Hb F. The β-globin haplotype and co-existing α-thal trait did not have any significant influence on serum bilirubin levels. Patients on hydroxyurea were older, had lower Hb F, but higher mean serum bilirubin. The latter also was signifcantly higher among those with UGTIAI (AT)7 homozygosity. Conclusions: Apart from UGTIAI (AT)7 homozygosity, Hb F, age and gender are the other factors that significantly influence serum bilirubin level in SCA. [ABSTRACT FROM AUTHOR]