Study on spectrum of UGT1A1 mutations in connection with inherited non-hemolytic unconjugated hyperbilirubinemia
10.3760/cma.j.issn.1007-3418.2018.12.005
- VernacularTitle: 遗传性非溶血性非结合型胆红素血症UGT1A1突变谱研究
- Author:
Qingfang XIONG
1
;
Yandan ZHONG
;
Xiaoning FENG
;
Hui ZHOU
;
Duxian LIU
;
Xuping WU
;
Yongfeng YANG
Author Information
1. Liver Disease Department, Nanjing Second Hospital, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, China
- Publication Type:Journal Article
- Keywords:
Heredity;
Gilbert Disease;
Crigler-Najjar syndrome;
UGT1A1
- From:
Chinese Journal of Hepatology
2018;26(12):898-902
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To compare and analyze patient’s general condition, changes in laboratory parameters, and the spectrum of UGT1A1 mutations in patients with inherited non-hemolytic unconjugated hyperbilirubinemia.
Methods:A retrospective study was conducted at Nanjing Second Hospital from January 2015 to July 2018 and patients’ demographic characteristics, liver function test, and UGT1A1 gene were analyzed. The categorical variable data were compared by χ 2 test. The normal distribution continuous variable data were compared by t-test and the non-normal distribution continuous variable data were compared using Mann-Whitney U test.
Results:Of the 51 patients with inherited non-hemolytic unconjugated hyperbilirubinemia, 44 (86.3%) were Gilbert’s syndrome (GS) and seven (13.7%) were Crigler-Najjar syndrome type II (CNS- II). The male to female ratio was 2.9:1 and the average age was 36.11 ± 13.17 years. Six variant types were detected: C. -40_-39insTA, C. -3279T > G, c.211G > A (p.G71R), c.686C > A (p.P229Q), c.1091C > T (p.P364L), c.1456T > G (P.Y486D). Among them, c.211G > A accounted for 58.82% (30/51), c.-40_-39insTA accounted for 27.5% (14/51), and c.1456T > G accounted for 25.5% (13/51). The total bilirubin(TB) and unconjugated bilirubin (UCB) in CNS-II patients were significantly higher than GS patients[155.91 (130 ~ 207) vs. 38.25(29 ~ 52.15) μmol/L, U = 0, P < 0.01; 144.13 (120.8 ~ 197) vs. 30.00 (21.7 ~ 46.75) μmol/L, U = 0.00, P < 0.01, respectively]. Exon mutations of c.1091C > T and c.1456T > G were statistically significant(P < 0.01).There were no differences in age, TB, UCB, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the c.211G > A homozygous variants and heterozygous variants (P > 0.05).
Conclusion:The common pathogenic mutations of UGT1A1 gene were c.211G > A, c.-40_-39insTA, c.1456T > G. c.211G > A. The mutation has little effect on the level of total bilirubin, but c.1091C > T, c.1456T > G mutations has great influence on the level of total bilirubin.
