Sampietro M, Lupica L, Perrero L, Romano R, Molteni V, Fiorelli G
Department of Internal Medicine, University of Milan, Italy.
Ital J Gastroenterol Hepatol. 1998 Apr;30(2):194-8.
A mutation in the promoter of the uridine diphosphate glucuronosyltransferase gene has been described in patients with Gilbert's syndrome from Northern Europe.
To assess the frequency of this mutation in Italian patients with Gilbert's syndrome and in normal controls, in order to establish the molecular basis and molecular epidemiology of the syndrome in Italy.
Forty-six patients with a clinical diagnosis of Gilbert's syndrome and 44 individuals from the general population unselected for bilirubin levels.
Polymerase chain reaction amplification of the TATA-box element in the promoter of uridine diphosphate glucuronosyltransferase and identification of wild-type and variant alleles by high-resolution polyacrylamide gel electrophoresis.
A TATA-box variant in the promoter of uridine diphosphate glucuronosyltransferase was found on 93% of chromosomes from patients with Gilbert's syndrome. The same variant was present on 44% of chromosomes from controls, unselected for bilirubin levels. Only 55% of controls homozygous for the TATA-box variant, however, had increased bilirubin levels.
The TATA-box variant in the promoter of uridine diphosphate glucuronosyltransferase is strongly associated with the phenotype of Gilbert's syndrome in Italy. The incomplete penetrance of the mutation observed in controls indicates that other acquired or inherited conditions affecting bilirubin production, uptake, cellular transport or excretion may contribute to the hyperbilirubinaemia of Gilbert's syndrome.
在北欧患有吉尔伯特综合征的患者中，已发现尿苷二磷酸葡萄糖醛酸转移酶基因启动子存在突变。
评估该突变在意大利吉尔伯特综合征患者及正常对照中的发生频率，以确定意大利该综合征的分子基础和分子流行病学特征。
46例临床诊断为吉尔伯特综合征的患者以及44名未根据胆红素水平进行筛选的普通人群个体。
对尿苷二磷酸葡萄糖醛酸转移酶启动子中的TATA盒元件进行聚合酶链反应扩增，并通过高分辨率聚丙烯酰胺凝胶电泳鉴定野生型和变异等位基因。
在吉尔伯特综合征患者93%的染色体上发现了尿苷二磷酸葡萄糖醛酸转移酶启动子中的TATA盒变异。在未根据胆红素水平进行筛选的对照中，44%的染色体上存在相同变异。然而，在TATA盒变异纯合的对照中，只有55%的个体胆红素水平升高。
在意大利，尿苷二磷酸葡萄糖醛酸转移酶启动子中的TATA盒变异与吉尔伯特综合征的表型密切相关。在对照中观察到的突变不完全外显表明，其他影响胆红素产生、摄取、细胞转运或排泄的获得性或遗传性状况可能导致吉尔伯特综合征的高胆红素血症。
