Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury

TY - JOUR

T1 - Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury

AU - Donaldson, Peter T.

AU - Daly, Ann K.

AU - Henderson, Jill

AU - Graham, Julia

AU - Pirmohamed, Munir

AU - Bernal, William

AU - Day, Christopher P.

AU - Aithal, Guruprasad P.

PY - 2010/12

Y1 - 2010/12

N2 - Background & Aims Co-amoxiclav is one of the most common causes of drug-induced liver injury (DILI) Although there are previous reports of genetic associations between HLA class II and co-amoxiclav-related DILI studies to date have been based on very small numbers from single centres only In order to address this problem we have investigated the role of HLA class II DRB1 and DQB1 in 61 cases of co-amoxiclav DILI as part of a UK-wide multi-centre study Methods HLA alleles and genotypes were compared with those of 40 individuals exposed to co-amoxiclav without toxicity (treated controls) and 191 population controls Results There were two significant findings from the study First HLA-DRB1*15 was increased in patients (53%) versus both treated (33% OR = 2 29 95% CI 1 00-5 26) and population controls (30% OR = 2 59 95% Cl 1 44-468 p = 0 002) Second DRB1*07 was found to be reduced in patients (9 8%) compared to both treated (35% OR = 018 95% Cl 006 - 052 p = 0 0011 pc = 0 0154) and population controls (29% OR = 0 266 95% Cl 011 - 065 p = 0 0019 pc = 0 0266) Conclusions These results confirm the previously reported significant genetic risk for HLA-DRB1*15 and also provide evidence of a protective effect of the HLA-DRB1*07 family of alleles HLA alleles and haplotypes may be particularly Important in susceptibility and iesistance to co-amoxiclav-DILI but It remains to be seen whether this effect is due to the identified alleles or others in close linkage disequilibrium elsewhere on the MHC (C) 2010 European Association for the Study of the Liver Published by Elsevier B V All rights reserved

AB - Background & Aims Co-amoxiclav is one of the most common causes of drug-induced liver injury (DILI) Although there are previous reports of genetic associations between HLA class II and co-amoxiclav-related DILI studies to date have been based on very small numbers from single centres only In order to address this problem we have investigated the role of HLA class II DRB1 and DQB1 in 61 cases of co-amoxiclav DILI as part of a UK-wide multi-centre study Methods HLA alleles and genotypes were compared with those of 40 individuals exposed to co-amoxiclav without toxicity (treated controls) and 191 population controls Results There were two significant findings from the study First HLA-DRB1*15 was increased in patients (53%) versus both treated (33% OR = 2 29 95% CI 1 00-5 26) and population controls (30% OR = 2 59 95% Cl 1 44-468 p = 0 002) Second DRB1*07 was found to be reduced in patients (9 8%) compared to both treated (35% OR = 018 95% Cl 006 - 052 p = 0 0011 pc = 0 0154) and population controls (29% OR = 0 266 95% Cl 011 - 065 p = 0 0019 pc = 0 0266) Conclusions These results confirm the previously reported significant genetic risk for HLA-DRB1*15 and also provide evidence of a protective effect of the HLA-DRB1*07 family of alleles HLA alleles and haplotypes may be particularly Important in susceptibility and iesistance to co-amoxiclav-DILI but It remains to be seen whether this effect is due to the identified alleles or others in close linkage disequilibrium elsewhere on the MHC (C) 2010 European Association for the Study of the Liver Published by Elsevier B V All rights reserved

M3 - Article

SN - 1600-0641

VL - 53

SP - 1049

EP - 1053

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 6

ER -