Relationship between UGT1A1 mutation and occurrence of Gilbert's syndrome

1.UGT1A1基因在日本人群中的突变和多态性分析了健康日本志愿者的UGT1A1基因。G71R的等位基因频率为13.8%，Y4860的等位基因频率为0，TA插入启动子TATA盒的频率为12.9%。这些结果与高加索人不同，编码区域很少发生突变，约16%的等位基因存在TA插入。2.分析了健康志愿者、Gilbert综合征和Crigler-Najjar综合征II型患者UGT1A1基因突变与血清胆红素水平的关系，并与血清胆红素水平进行了比较。在健康志愿者中，UGT1A1突变多为杂合性TA插入(位于启动子的TATA盒中)或杂合性G71R。在Gilbert综合征患者中，除TA插入和G71R外，还发现了各种错义突变，并发现了新的错义突变P364L，表达的酶活性正在研究中。III型Crigler-Najjar综合征患者存在纯合子错义突变。UGT1A1突变与空腹高胆红素血症的关系。低热量试验是诊断Gilbert综合征的常用方法。健康志愿者和Gilbert综合征患者24小时卡路里摄入量限制在4O0卡路里，并观察了基因突变与血清胆红素水平升高的关系。UGT1A1任何突变的受试者在健康志愿者和Gilbert综合征患者的血清胆红素水平均显著升高(超过0.6 mg/dl)。

l.UGT1A1 gene mutation and polymorphism in Japanese populationUGT1A1 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 levelUGT1A1 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 hyperbilirubinemiaLow 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.