Co-inherited Gilbert's syndrome: a factor determining hyperbilirubinemia in homozygous beta-thalassemia

Background and Objective. Patients with thalassemia major and intermedia sh ow a marked variability of serum indirect bilirubin levels. In this paper w e tested the hypothesis related to the variability of the glucuronidation b ilirubin rate which depends on the configuration of the A(TA)(n)TAA motif o f the UGT1*1 glucuronosyltransferase gene promoter. Design and Methods. We studied the configuration of the A(TA)(n)TAA motif i n 26 patients with thalassemia major and 34 with thalassemia intermedia. Results. In patients with thalassemia major and in those with thalassemia I ntermedia significantly higher bilirubin levels were found in patients with the (IA)(7)/(TA)(7) genotype, than in those with the (TA)(7)/(TA)(6) or (T A)(6)/(TA)(6) genotype. Interpretation and Conclusions. These results indicate that the (TA)(7)/(TA )(7) genotype, the configuration found in patients with Gilbert's syndrome, is capable of modifying the clinical phenotype of homozygous beta-thalasse mia. This is an example of the role played by co-inherited modifying gene(s ) on the extent of clinical heterogeneity of monogenic disorders. (C)1999, Ferrata Storti Foundation.