Co-inherited Gilbert's syndrome: a factor determining hyperbilirubinemia in homozygous beta-thalassemia.
OBJECTIVE
Patients with thalassemia major and intermedia show a marked variability of serum indirect bilirubin levels. In this paper we tested the hypothesis related to the variability of the glucuronidation bilirubin rate which depends on the configuration of the A(TA)nTAA motif of the UGT1*1 glucuronosyltransferase gene promoter.


METHODS
We studied the configuration of the A(TA)nTAA motif in 26 patients with thalassemia major and 34 with thalassemia intermedia.


RESULTS
In patients with thalassemia major and in those with thalassemia intermedia significantly higher bilirubin levels were found in patients with the (TA)7/(TA)7 genotype, than in those with the (TA)7/(TA)6 or (TA)6/(TA)6 genotype.


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-thalassemia. This is an example of the role played by co-inherited modifying gene(s) on the extent of clinical heterogeneity of monogenic disorders.
Galanello
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R
Istituto di Clinica e Biologia dell'Età Evolutiva, Università degli Studi di Cagliari, Ospedale Regionale Microcitemie, Italy. renzo.galanello@mcweb.unica.it
Cipollina
M D
MD
Dessì
C
C
Giagu
N
N
Lai
E
E
Cao
A
A
D005878:Gilbert Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D006932:Hyperbilirubinemia / Q000235:genetics*; D012307:Risk Factors; D013577:Syndrome; D017086:beta-Thalassemia / Q000235:genetics*