Ivanov Andrei, Semenova Elena
Human Genetics Department, Saint-Petersburg State University Hospital, 154, Fontanka River Embankment, St.Petersburg, 198103, Russia.
Division of Molecular and Radiation Biophysics, National Research Center "Kurchatov Institute" B.P.Konstantinov St Petersburg Nuclear Physics Institute, Gatchina, 188300, Russia.
J Clin Exp Hepatol. 2021 Nov-Dec;11(6):691-699. doi: 10.1016/j.jceh.2021.01.006. Epub 2021 Feb 4.
BACKGROUND/OBJECTIVES: Gilbert's syndrome (GS) is a hereditary pathology that affects approximately 10% of the world's population. In most cases, GS is associated with the polymorphism of gene coding the enzyme bilirubin uridine diphosphate glucuronosyltransferase (UGT-1A) which plays a key role in the bilirubin metabolism. The presence of an additional TA repeat in the TATA box of the gene promoter (the allelic variant of 7TA, abbreviated as ) leads to a significant decrease in the enzymatic activity of UGT-1A in the liver and to decrease in glucuronidation process as a consequence. The aim of the study is to estimate the prevalence of the 6TA/6TA, 6TA/7TA, and 7TA/7TA genotypes of promoter and to analyze the effect of these variants on bilirubin levels in healthy men in North-West Russia and patients with a clinical diagnosis of GS.
Genotyping of the ∗28 (rs8175347) polymorphism was carried out by real-time PCR.
The results obtained indicate an increased probability of GS developing in residents of the North-West region of Russia compared with other representatives of the Caucasians.
Despite the fact that the level of serum bilirubin increases with the rise in the number of additional TA dinucleotides in the gene promoter tests of clinical manifestations only (jaundice, fatigue, sleep disturbances, nausea, belching, and so on) and increased bilirubin levels in patients with normal liver function do not allow unequivocally diagnose GS. genotyping should be used as a prognostic risk factor for such pathology development.
背景/目的：吉尔伯特综合征（GS）是一种遗传性疾病，全球约10%的人口受其影响。在大多数情况下，GS与编码胆红素尿苷二磷酸葡萄糖醛酸转移酶（UGT-1A）的基因多态性有关，该酶在胆红素代谢中起关键作用。基因启动子的TATA框中额外的TA重复序列（等位基因变体7TA，简称为 ）的存在导致肝脏中UGT-1A的酶活性显著降低，进而导致葡萄糖醛酸化过程减少。本研究的目的是评估 启动子的6TA/6TA、6TA/7TA和7TA/7TA基因型的患病率，并分析这些变体对俄罗斯西北部健康男性和临床诊断为GS的患者胆红素水平的影响。
通过实时聚合酶链反应对 ∗28（rs8175347）多态性进行基因分型。
所得结果表明，与其他高加索人相比，俄罗斯西北部居民患GS的可能性增加。
尽管血清胆红素水平会随着基因启动子中额外TA二核苷酸数量的增加而升高，但仅靠临床表现测试（黄疸、疲劳、睡眠障碍、恶心、嗳气等）以及肝功能正常患者胆红素水平升高并不能明确诊断GS。基因分型应用作此类疾病发展的预后风险因素。
