Restriction fragment length polymorphism effectively identifies exon 1 mutation of UGT1A1 gene in patients with Gilbert's Syndrome. (6th February 2015)

• Record Type: Journal Article
• Authors: Shiu, Tzu‐Yue; Huang, Hsin‐Hung; Lin, Hsuan‐Hwai; Shih, Yu‐Lueng; Chu, Heng‐Cheng; Chang, Wei‐Kuo; Hsieh, Tsai‐Yuan
• Is Part Of: Liver international. Volume 35:Number 8(2015:Aug.)
• Page Start: 2050
• Page End: 2056
• Publication Date: 2015-02-06
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12785
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12785-abs-0001"> <title>Abstract</title> <sec id="liv12785-sec-0001" sec-type="section"> <title>Background & Aims</title> <p>Gilbert's syndrome causes pharmacological variation in drug glucuronidation and unexpected toxicity from therapeutic agents. The two common genotypes of Gilbert's syndrome are a dinucleotide polymorphism (TA)<sub>7</sub> in TATA‐Box as well as the 211G>A mutation in the coding exon 1, particularly in Asians, of human <italic>UGT1A1</italic> gene. In this study, we aimed to establish an effective method to detect the 211G>A mutation.</p> </sec> <sec id="liv12785-sec-0002" sec-type="section"> <title>Methods</title> <p>The coding exon 1 sequence of human <italic>UGT1A1</italic> gene was analysed by Vector NTI software. The 211G>A mutation in the coding exon 1 of <italic>UGT1A1</italic> gene was determined by restriction fragment length polymorphism (RFLP) method. Serum total bilirubin level was measured as well.</p> </sec> <sec id="liv12785-sec-0003" sec-type="section"> <title>Results</title> <p>A newly identified BsmBI site was located in the coding exon 1 of <italic>UGT1A1</italic> gene. The 211G>A mutation in the coding exon 1 of <italic>UGT1A1</italic> gene was determined by DNA RFLP. Furthermore, we reported our present work on genetic analysis of mutations of <italic>UGT1A1</italic> gene, and the correlation of <italic>UGT1A1</italic> mutations with serum total bilirubin levels in Taiwanese population. The results showed that 15 subjects carried 211G>A mutation in 23 subjects related with Gilbert's syndrome. The homozygous 211G>A mutant as well as simultaneously heterozygous mutants both in TATA‐Box and 211G>A significantly increased the risk of Gilbert's syndrome similar to subjects carrying homozygous TATA‐Box mutant.</p> </sec> <sec id="liv12785-sec-0004" sec-type="section"> <title>Conclusions</title> <p>BsmBI RFLP is an effective method to detect 211G>A mutation in the coding exon 1 of <italic>UGT1A1</italic> gene. The common 211G>A mutation is one of the causes of Gilbert's syndrome in Taiwanese population.</p> </sec> </abstract>