[A study of polymorphism in UDP-glucuronosyltransferase 1 (UGT-1A1) promoter gene in Korean patients with Gilbert's syndrome].
OBJECTIVE
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).


CONCLUSIONS
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.
Kim
Yoon Hong
YH
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. ynree@kumc.or.kr
Yeon
Jong Eun
JE
Jung
Gil Man
GM
Kim
Hyo Jung
HJ
Kim
Jae Seon
JS
Byun
Kwan Soo
KS
Bak
Young Tae
YT
Lee
Chang Hong
CH
D000328:Adult; D005260:Female; D005878:Gilbert Disease / Q000201:enzymology / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007723:Korea; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme