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The association between HLA-DQB1 polymorphism and antituberculosis drug-induced liver injury: a Case-Control Study
Chen, R.1; Zhang, Y.1,2; Tang, S.1,3; Lv, X.1,4,5; Wu, S.1; Sun, F.1; Xia, Y.6; Zhan, S. Y.1
关键词antituberculosis drug-induced liver injuries antituberculosis treatment case-control study HLA pharmacogenetics
刊名JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
2015-02-01
DOI10.1111/jcpt.12211
40期:1页:110-115
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; National Natural Science Foundation of China ; Beijing Natural Science Foundation
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]NECROSIS-FACTOR-ALPHA ; CLASS-II GENOTYPE ; INDUCED HEPATOTOXICITY ; INDUCED HEPATITIS ; RISK-FACTORS ; GENOME-WIDE ; PULMONARY TUBERCULOSIS ; HLA ; SUSCEPTIBILITY ; ALLELES
英文摘要

What is known and objectiveResearch on genetic factors associated with antitubercular drug-induced liver injuries (ATLI) has been reported. However, most of the research has focused on genetic polymorphisms of genes encoding metabolic enzymes, including NAT2, GST and CYP450. It is probable that the immune system also contributes to the onset of drug adverse effects. A few small studies have explored the possible association of HLA genes with drug-induced liver injuries (DILI), but more supportive evidence from larger studies or prospective cohort designs is needed. We aim to explore the possible association of HLA-DQB1 gene polymorphisms with ATLI in a case-control study.

MethodsA case-control study design was used. ATLI was recorded in a prospectively followed-up cohort of patients receiving antituberculosis treatment. Identified cases were matched with control tuberculosis patients within the same cohort but with no adverse effects in 1:1 ratio. We used the sequence-based typing method to determine the HLA-DQB1 genotypes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression.

Results and discussionEighty-nine cases were included in this case-control study. HLA-DQB1 typing was successful for 177 subjects. No association between frequency of HLA-DQB1 genotypes and ATLI was statistically significant in univariate analyses. Multivariate analysis using the conditional logistic regression model revealed that the individuals with two DQB1*05 alleles were at higher risk of ATLI than control subjects. The OR was 528 adjusted for use of liver protective drugs and weight (10/88 VS 2/88, 95% CI: 1134-24615, P=0034). Analysis according to the liver injury type showed that both mixed liver injury patients and cholestatic/mixed liver injury patients had higher proportions of DQB1*05:02 alleles (P values were 0028 and 0005, respectively).

What is new and conclusionThis study suggests that ATLI was more likely in subjects of HLA-DQB1*05/*05 genotype. Further studies are needed to verify this association.

语种英语
所属项目编号81072387 ; 7111006
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; National Natural Science Foundation of China ; Beijing Natural Science Foundation
WOS记录号WOS:000347240200017
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58609
专题北京大学公共卫生学院
作者单位1.Peking Univ Hlth Sci Ctr, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing 100191, Peoples R China
2.McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada
3.Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China
4.Peking Univ Inst Mental Hlth, Div Clin Res, Beijing, Peoples R China
5.Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China
6.Chinese Ctr Dis Control & Prevent, Natl Ctr TB Control & Prevent, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Chen, R.,Zhang, Y.,Tang, S.,et al. The association between HLA-DQB1 polymorphism and antituberculosis drug-induced liver injury: a Case-Control Study[J]. JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS,2015,40(1):110-115.
APA Chen, R..,Zhang, Y..,Tang, S..,Lv, X..,Wu, S..,...&Zhan, S. Y..(2015).The association between HLA-DQB1 polymorphism and antituberculosis drug-induced liver injury: a Case-Control Study.JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS,40(1),110-115.
MLA Chen, R.,et al."The association between HLA-DQB1 polymorphism and antituberculosis drug-induced liver injury: a Case-Control Study".JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS 40.1(2015):110-115.
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