| Research Abstract |
l.UGT1A1 gene mutation and polymorphism in Japanese population
UGT1A1 gene was analysed in healthy Japanese volunteers. Allelic incidence for G71R was 13.8 %, that for Y4860 was 0 %, and that for TA insertion into the TATA box of the promoter was 12.9 %.
These results were different from those of the Caucasians, i.e., mutation in the coding region is seldom found and the TA insertion is found in about 16 % of the alleles.
2.Relationship between UGT1A1 mutation and serum bilirubin level
UGT1A1 gene was analyzed in healthy volunteers and the patients with Gilbert's syndrome and with Crigler-Najjar syndrome type II, and compared the results with their serum bilirubin levels. Most of the UGT1A1 mutation in the healthy volunteers were heterozygous TA insertion (into the TATA box of the promoter)or heterozygous G71R.In the patients with Gilbert's syndrome, various mis-sense mutations were found in the ceding region in addition to the TA insertion and G71R.New mis-sense mutaion, P364L, was found and the expressed enzyle activity is now under investigation. Homzygous mis-sense mutations were found in the patients with Crigler-Najjar syndrome type II.
3.Relationship between UGT1A1 mutation and fasting hyperbilirubinemia
Low calory test is commonly used for diagnosis of Gilbert's syndrome. Calory intake was restricted to 4O0 Calories for 24 hours in healthy volunteers and the patients vith Gilbert's syndrome, and relationship was observed between the gene mutation and elevation of seru bilirubin levels. Subjects with any mutation in UGT1A1 showed marked elevation(more than 0.6 mg/dl)of serum bilirubin both in the healthy volunteers and in the patients with Gilbert's syndrome.
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