Identifying UGT1A1 gene mutations in Vietnamese patients with Gilbert syndrome

Abstract

Gilbert's syndrome (GS) is the most common inherited disorder of bilirubin metabolism, non-lethal, affecting 3-12% of the population. The genetic variants of the UDP- glucuronosyltransferase 1A1 (UGT1A1) gene might reduce the gene transcription activity and its enzyme expression, which affects the ability to conjugate glucuronidation in the liver. This study aimed to identify genetic variants of UGT1A1 in two Vietnamese sibling brothers with jaundice manifestations suspected GS. The peripheral blood samples of patients were used to extract genome DNA and sequence the enhancer, promoter, and coding all five exons s of UGT1A1. Two pathogenic variants c.-3279T>G located in the phenobarbital responsive enhancer module (gtPBREM) and A(TA)₇TAA of the TATA box in the promoter region were identified. They are twice common pathogenic variants that were reported in almost hyperbilirubinemia individuals from different populations. The obtained results improved the accuracy of medical diagnosis and warned the patients to be cautious in case they have to use medical drugs in the future.