Study on the relationship between UGT1A1 polymorphism and UGT1A1 inhibitory drugs-induced liver injury
10.3969/j.issn.1006-5725.2025.04.019
- VernacularTitle:UGT1A1多态性与UGT1A1抑制药物相关药物性肝损伤的关系
- Author:
Yujia LU
1
;
Keying OU
;
Yueyang MA
;
Chuansu YUAN
;
Bin LIU
;
Yongfeng YANG
;
Qingfang XIONG
Author Information
1. 南京中医药大学附属南京医院(南京市第二医院)肝病科(江苏 南京 210003);南京市传染病临床中心(江苏 南京 210003)
- Publication Type:Journal Article
- Keywords:
drug-induced liver injury;
gene polymorphism;
UGT1A1;
drug;
inhibitor
- From:
The Journal of Practical Medicine
2025;41(4):588-593
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the association between UGT1A1 inhibitors-induced liver injury(DILI)and UGT1A1 gene polymorphisms through a pharmacogenomics approach.Methods Information on relevant drugs that may induce liver injury,blood routine tests,and liver function tests was collected from hospitalized patients diagnosed with DILI between June 2022 and June 2024.Relevant databases were searched to categorize DILI-associated drugs into UGT1A1 enzyme inhibitors and those without interaction with UGT1A1.Sanger sequenc-ing or MassARRAY SNP typing technology was utilized to detect and genotype the UGT1A1 gene.Results A total of 219 patients with drug-induced liver injury(DILI)were enrolled,including 98 males,with a mean age of 46.32±14.95 years.A literature search of relevant databases revealed that 20 drugs(16.26%,20/123)associated with DILI had inhibitory effects on the UGT1A1 enzyme.The proportion of DILI cases related to UGT1A1 inhibitors was 60.73%(133/219).Compared to non-UGT1A1 inhibitor-related DILI group,the UGT1A1 inhibitor-related DILI group exhibited significantly higher levels of ALT,AST,ALP,and GGT(P<0.05),while no significant differences were observed in age,gender,TBIL,IBIL,WBC,Hb,PLT,injury type,or injury grade(P>0.05).The prevalence of UGT1A1 polymorphisms was significantly higher in the UGT1A1 inhibitor-related DILI group(68.42%)com-pared to the non-UGT1A1 inhibitor-related DILI group(51.16%),with an odds ratio(OR)of 2.068(95%CI:1.183 to 3.617;χ2=6.58,P=0.010).There was also a significant difference in the distribution of genotypes between the UGT1A1 inhibitor-related and non-UGT1A1 inhibitor-related DILI groups(χ2=9.60,P=0.022).Univariate logistic regression analysis indicated that ALT and UGT1A1*6 were associated with UGT1A1 inhibitor-related DILI,while multivariate analysis confirmed that UGT1A1*6 was independently associated with UGT1A1 inhibitor-related DILI[OR(95%CI)=3.143(1.398 to 7.067),P=0.006].Conclusion The UGT1A1*6 allele increases the susceptibility to drug-induced liver injury(DILI)associated with UGT1A1 inhibitory drugs.
