Ostanek Barbara, Furlan Danijela, Mavec Tina, Lukac-Bajalo Jana
University of Ljubljana, Faculty of Pharmacy, Department of Clinical Biochemistry, Askerceva 7, SI-1000 Ljubljana, Slovenia.
Blood Cells Mol Dis. 2007 Mar-Apr;38(2):78-82. doi: 10.1016/j.bcmd.2006.10.160. Epub 2006 Dec 28.
Gilbert's syndrome is a mild hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin UDP-glucuronosyltransferase gene (UGT1A1). The causative mutation in Caucasians is almost exclusively a TA dinucleotide insertion in the TATA box of the UGT1A1 promoter. Affected individuals are homozygous for the variant promoter and have 7 instead of 6 TA repeats. The aim of the present study was to determine the genotypes of UGT1A1(TA)n promoter polymorphism in the healthy Slovenian population and to investigate the association of genotypes with serum bilirubin levels. 236 healthy subjects were genotyped by single-strand conformation polymorphism analysis, which was validated by sequence analysis. The frequencies of genotypes were as follows: (TA)(6/6) (38.1%), (TA)(6/7) (47.9%), (TA)(7/7) (13.6%). There was a statistically significant association of genotypes with serum bilirubin levels (p<0.001). Subjects with genotype (TA)(7/7) had the highest and subjects with genotype (TA)(6/6) the lowest total serum bilirubin levels. One individual in the group had the rare genotype (TA)(7/8) (0.4%). Analysis of his family showed the following genotypes: (TA)(6/8) in his father and sister and (TA)(7/8) in his two brothers. In conclusion, the frequency of UGT1A1(TA)n promoter polymorphism genotypes was determined for the first time in the Slovenian population and is similar to frequencies observed in other Caucasian populations. The extremely rare (TA)8 allele in Caucasians was found also in Slovenians.
吉尔伯特综合征是一种由胆红素UDP - 葡萄糖醛酸基转移酶基因（UGT1A1）突变引起的轻度遗传性非结合胆红素血症。白种人中的致病突变几乎完全是UGT1A1启动子TATA框中的TA二核苷酸插入。受影响个体的变异启动子为纯合子，有7个而非6个TA重复序列。本研究的目的是确定健康斯洛文尼亚人群中UGT1A1(TA)n启动子多态性的基因型，并研究基因型与血清胆红素水平的关联。通过单链构象多态性分析对236名健康受试者进行基因分型，并通过序列分析进行验证。基因型频率如下：(TA)(6/6)（38.1%），(TA)(6/7)（47.9%），(TA)(7/7)（13.6%）。基因型与血清胆红素水平存在统计学显著关联（p<0.001）。基因型为(TA)(7/7)的受试者总血清胆红素水平最高，基因型为(TA)(6/6)的受试者最低。该组中有一名个体具有罕见的基因型(TA)(7/8)（0.4%）。对其家族的分析显示以下基因型：他的父亲和妹妹为(TA)(6/8)，他的两个兄弟为(TA)(7/8)。总之，首次在斯洛文尼亚人群中确定了UGT1A1(TA)n启动子多态性基因型的频率，且与其他白种人群中观察到的数据相似。斯洛文尼亚人中也发现了白种人中极其罕见的(TA)8等位基因。
