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Relationship between UGT1A1 mutation and occurrence of Gilbert's syndrome

UGT1A1突变与吉尔伯特综合征发生的关系

基本信息

批准号：
10470133
负责人：
ADACHI Yukihiko
金额：
$ 1.15万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

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.

1.日本人群UGT 1A 1基因突变和多态性分析G71 R的等位基因发生率为13.8%，Y 4860的等位基因发生率为0%，TA插入启动子TATA盒的等位基因发生率为12.9%。2. UGT 1A 1基因突变与血清胆红素水平的关系分析了健康志愿者、吉尔伯特综合征和Crigler-Najjar综合征II型患者的UGT 1A 1基因，并与血清胆红素水平进行了比较。健康人UGT 1A 1基因突变多为杂合性TA插入（插入启动子的TATA盒）或杂合性G71 R;吉尔伯特综合征患者除TA插入和G71 R外，还发现多种错义突变，并发现新的错义突变P364 L，其表达的酶活性正在研究中。II型Crigler-Najjar综合征患者存在UGT 1A 1基因纯合突变。3. UGT 1A 1基因突变与空腹高胆红素血症的关系低热量试验是诊断吉尔伯特综合征的常用方法。对健康志愿者和吉尔伯特综合征患者24小时限制热量摄入400卡，观察基因突变与血清胆红素水平升高的关系。在健康志愿者和吉尔伯特综合征患者中，UGT 1A 1任何突变的受试者均显示血清胆红素显著升高（超过0.6 mg/dl）。