BACKGROUNDS/AIMS: Hepatic glucuronidating activity, essential for efficient biliary excretion of bilirubin, is reduced to about 30 percent of normal in patients with Gilbert's syndrome. Patients with Gilbert's syndrome have an additional TA insertion in the A(TA)TAA of UDP-glucuronosyltransferase 1 (UGT-1A1) promoter gene. This results in reduced frequency and accuracy of transcription initiation and enzyme activity. The frequency and location of the mutation vary according to races. This study was done to determine the UGT-1A1 promoter gene mutation in Korean cases of Gilbert's syndrome. METHODS: Promoter regions of the gene for bilirubin UGT-1A1 in twelve patients with Gilbert's syndrome and twenty healthy subjects (controls) were sequenced. RESULTS: 1) Among twelve Gilbert's syndrome five patients were homozygous for A(TA)6/6TAA, two were homozygous for A(TA)7/7TAA, and the other five were heterozygous for A(TA)6/7TAA. The prevalence of A(TA)TAA mutation was 58.3 percent. 2) Among twenty healthy subjects seventeen were homozygous for A(TA)6/6TAA, one was homozygous for A(TA)7/7TAA, and two were heterozygous for A(TA)6/7TAA. The prevalence of A(TA)TAA mutation was 15 percent. 3) The prevalence of A(TA)TAA mutation in Gilbert's syndrome patients was significantly higher than in the controls (p=0.018). CONCLUSION: Although the prevalence of A(TA)TAA mutation in Korean patients with Gilbert's syndrome is significantly higher than in the controls, the mutations of the promoter region of UGT-1A1 gene appear not to be the main or sole cause in Gilbert's syndrome in Korea since the prevalence of A(TA)TAA mutation is not so high. Further studies to determine the relationship between other UGT-1A1 gene mutation and Gilbert's syndrome in Korea are needed.
Adult ; English Abstract ; Female ; Gilbert Disease/enzymology/*genetics ; Glucuronosyltransferase/*genetics ; Human ; Korea ; Male ; *Mutation ; *Polymorphism (Genetics) ; Promoter Regions (Genetics)/*genetics