Dabke Pooja S, Colah Roshan B, Ghosh Kanjaksha K, Nadkarni Anita H
Hematology. 2014 Oct;19(7):388-92. doi: 10.1179/1607845413Y.0000000142. Epub 2013 Nov 30.
Gilbert syndrome is characterized by mild unconjugated hyperbilirubinemia. The high levels of bilirubin could be related to the co-inheritance of Gilbert syndrome determined either by mutations of the coding region or by variation in the (TA)n motifs of the promoter region of the bilirubin UGT1A1 gene. The co-inheritance of Gilbert syndrome has been reported to elevate bilirubin levels in beta thalassemia and sickle cell disease patients. Aim In this study, we have tried to investigate whether the variability in serum bilirubin levels found in transfusion-dependent beta thalassemia, beta thalassemia intermedia, and heterozygous beta thalassemia individuals could be related to the coexistence of Gilbert syndrome.
The promoter region (TA)n motifs of the bilirubin UGT1A1 gene were analyzed in 104 beta thalassemia individuals. The control group consisted of 50 healthy individuals.
The analysis of the UGT1A1 promoter showed three (TA) motifs: (TA)5, (TA)6, and (TA)7. The frequency of genotype (TA)7/(TA)7 did not differ significantly between the groups studied. A significant difference was observed in mean serum bilirubin levels between individuals showing (TA)7/(TA)7 and (TA)6/(TA)6 genotypes and also between (TA)7/(TA)7 and (TA)6/(TA)7 genotypes among all groups studied. According to the beta genotype, no differences were observed between mean serum bilirubin levels in the three groups (β(+)/β(+), β(0)/β(+), and β(0)/β(0)).
These results indicate that the (TA)7/(TA)7 configuration is one of the factors responsible for hyperbilirubinemia and, therefore, seems to interfere with the clinical expression of homozygous beta thalassemia. This emphasizes the role played by co-inherited modifying genes on clinical heterogeneity of monogenic disorders.
吉尔伯特综合征的特征是轻度非结合性高胆红素血症。胆红素水平升高可能与吉尔伯特综合征的共同遗传有关，这是由编码区突变或胆红素UGT1A1基因启动子区(TA)n基序的变异所决定的。据报道，吉尔伯特综合征的共同遗传会使β地中海贫血和镰状细胞病患者的胆红素水平升高。目的：在本研究中，我们试图调查在依赖输血的β地中海贫血、中间型β地中海贫血和杂合子β地中海贫血个体中发现的血清胆红素水平变化是否与吉尔伯特综合征的共存有关。
对104例β地中海贫血个体的胆红素UGT1A1基因启动子区(TA)n基序进行分析。对照组由50名健康个体组成。
UGT1A1启动子分析显示有三个(TA)基序：(TA)5、(TA)6和(TA)7。所研究的组间基因型(TA)7/(TA)7的频率没有显著差异。在所有研究组中，显示(TA)7/(TA)7和(TA)6/(TA)6基因型的个体之间以及(TA)7/(TA)7和(TA)6/(TA)7基因型的个体之间，平均血清胆红素水平存在显著差异。根据β基因型，三组(β(+)/β(+)、β(0)/β(+)和β(0)/β(0))的平均血清胆红素水平没有差异。
这些结果表明，(TA)7/(TA)7构型是导致高胆红素血症的因素之一，因此似乎会干扰纯合子β地中海贫血的临床表现。这强调了共同遗传修饰基因在单基因疾病临床异质性中所起的作用。
