Analysis of the A(TA)nTAA configuration in the promoter region of the UGT1 A1 gene in Greek patients with thalassemia intermedia and sickle cell disease

Gilbert’s syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)nTAA configuration residing in the promoter region of the UGT1 A1 gene. This configuration may vary in length; the “n” represents the different number of TA repeats. The homozygosity A(TA)7TAA/A(TA)7TAA is involved in Gilbert’s syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)7TAA/A(TA)7TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for β thalassemia and sickle cell anemia. Analysis of the A(TA)nTAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)7TAA/A(TA)7TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert’s syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients.