UGT1A1 gene polymorphisms in patients with Gilbert syndrome and Crigler-Najjar syndrome type Ⅱ

Nianchen LIU; Jie BAI; Chen LIANG; Li BAI; Shuang LIU; Zhongping DUAN; Sujun ZHENG

doi:10.3969/j.issn.1001-5256.2022.02.026

Volume 38 Issue 2

Feb. 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(2): 397-401

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UGT1A1 gene polymorphisms in patients with Gilbert syndrome and Crigler-Najjar syndrome type Ⅱ

DOI: 10.3969/j.issn.1001-5256.2022.02.026

Nianchen LIU^1a,
Jie BAI^1a,
Chen LIANG^1a,
Li BAI²,
Shuang LIU²,
Zhongping DUAN^{1b, 2},
Sujun ZHENG^{1a
,
,}

1a.
First Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
1b.
Fourth Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
2.
Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing 100069, China

Research funding:

Project Charter for Development and Construction of Key Medical Specialties by Beijing Hospitals Authority (ZYLX202125);

Project of Coordinated Development Center for Gastroenterology in Beijing Municipal Administration of Hospitals (XXZ0503)

More Information

Corresponding author: ZHENG Sujun, zhengsujun003@126.com
Received Date: 2021-07-08
Accepted Date: 2021-09-01
Published Date: 2022-02-20

Abstract

Abstract

Objective To investigate the differences in UGT1A1 gene mutation sites, haplotypes, and diplotypes between patients with Gilbert syndrome (GS) and those with Crigler-Najjar syndrome type Ⅱ (CN-2). Methods A retrospective analysis was performed for the clinical data of 138 patients with GS or CN-2 who attended Beijing YouAn Hospital, Capital Medical University, from January 1, 2010 to December 31, 2019, with 109 patients in the GS group and 29 patients in the CN-2 group, and the differences in mutation sites were analyzed between the two phenotypes. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. SNPStats software was used to perform linkage disequilibrium (LD) and haplotype analyses of mutation sites. Strong LD was defined as both |D′| and r² > 0.8, and moderate LD was defined as |D′| > 0.8 and r² > 0.4. Results UGT1A1 gene detection was performed for all patients, and mutations mainly included -3279T > G mutation (104 patients, 75.36%) and -3152G > A mutation (82 patients, 59.42%) in the upstream promoter PBREM region, a promoter TATA box TA insertion mutation (88 patients, 63.77%), and c.211G > A mutation in Exon 1 of the coding region (66 patients, 47.83%). Compared with the CN-2 group, the GS group had a significantly higher proportion of PBREM region -3279T > G mutation (82.57% vs 48.28%, χ²=14.508, P < 0.001), PBREM region -3152G > A mutation (68.81% vs 24.14%, χ²=18.955, P < 0.001), and promoter TATA box (TA)₆ > (TA)₇ mutation (72.48% vs 31.03%, χ²=17.027, P < 0.001), and compared with the GS group, the CN-2 group had a significantly higher proportion of mutations at the c.211 locus (68.97% vs 42.20%, χ²=6.575, P=0.010) and the c.1456 locus (51.72% vs 7.34%, χ²=29.372, P < 0.001). LD analysis of different mutation sites of the UGT1A1 gene showed strong LD (|D′| > 0.8, r² > 0.8) between (TA)₆ > (TA)₇ and -3152G > A and moderate LD (|D′| > 0.8, r² > 0.4) between (TA)₆ > (TA)₇ and -3279T > G, between -3152G > A and -3279T > G, between (TA)₆ > (TA)₇ and c.211G > A, and between -3279T > G and c.211G > A. Haplotype frequency analysis showed that compared with the CN-2 group, the GS group had a significantly higher frequency of haplotype -3279G—-3152A—(TA)₇ (45.72% vs 17.24%, χ²=7.833, P=0.005) and significantly lower frequencies of c.1456G (4.10% vs 16.48%, χ²=4.873, P=0.027) and c.211A—c.1456G (1.86% vs 24.90%, χ²=15.210, P < 0.001). The diplotype analysis showed that diplotypes consisting of haplotype c.1456G or c.211A—c.1456G were associated with a higher level of total bilirubin (TBil). Conclusion There are differences in common mutation sites and major haplotypes of the UGT1A1 gene between patients with GS and those with CN-2, and the common diplotypes of CN-2 correspond to a higher level of TBil.
- Gilbert Disease,
- Crigler-Najjar Syndrome,
- Polymorphism, Genetic

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References

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UGT1A1 gene polymorphisms in patients with Gilbert syndrome and Crigler-Najjar syndrome type Ⅱ

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UGT1A1 gene polymorphisms in patients with Gilbert syndrome and Crigler-Najjar syndrome type Ⅱ

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