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The association between HLA ‐ DQB 1 polymorphism and antituberculosis drug‐induced liver injury: a Case–Control Study
Author(s) -
Chen R.,
Zhang Y.,
Tang S.,
Lv X.,
Wu S.,
Sun F.,
Xia Y.,
Zhan S. Y.
Publication year - 2015
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12211
Subject(s) - liver injury , medicine , human leukocyte antigen , drug , pharmacology , hla dqb1 , case control study , immunology , antigen
Summary What is known and objective Research 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 NAT 2, GST and CYP 450. 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 ‐ DQB 1 gene polymorphisms with ATLI in a case–control study. Methods A 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 ‐ DQB 1 genotypes. Odds ratios ( OR ) and 95% confidence intervals ( CI ) were calculated using conditional logistic regression. Results and discussion Eighty‐nine cases were included in this case–control study. HLA ‐ DQB 1 typing was successful for 177 subjects. No association between frequency of HLA ‐ DQB 1 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 5·28 adjusted for use of liver protective drugs and weight (10/88 VS 2/88, 95% CI : 1·134‐24·615, P = 0·034). 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 0·028 and 0·005, respectively). What is new and conclusion This study suggests that ATLI was more likely in subjects of HLA ‐ DQB 1*05/*05 genotype. Further studies are needed to verify this association.