| Research Abstract |
Patients with Gilbert's syndrome have mild, chronic unconjugated hyperbilirubinemia. Based on the bilirubin level in the blood, 3 to 10 percent of the general population are estimated to have Gilbert's syndrome. Hepatic glucuronidating activity, which is essential for efficient biliary excretion of bilirubin, is approximately 30 percent of normal in patients with Gilbert's syndrome. Genetic analysis showed that heterozygous mutation in bilirubin : UDP-glucuronosyltransferase gene was observed in patients with Gilbert's syndrome (Aono et al, Lancet, 345, 958-959, 1995), suggesting the dominant trait of inheritance. On the other hand, Bosma et al. (New Engl. J.Med., 333, 1171-1175, 1995) reported a homozygous abnormality in the promoter region of the gene (extra TA in TATA box) in patients with Gilbert's syndrome, indicating the recessive trait of the syndrome. In order to clarify the mechanism underlying the genetic inheritance of Gilbert's syndrome, we carried out a futther genetic analysis of patients and their families. All female patients so far examined had abnormalities on the both alleles. Some male patients also had abnormalities on the both alleles. However, interestingly enough, the rest of the male patients had abnormalities only in either allele. These findings suggest that other factor(s) besides the gene abnormality is necessary for the complete manifestation of the syndrome in male.
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