title: Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury.
abstract: OBJECTIVE
  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 multicentre 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% CI: 1.44-4.68: p=0.002). Second, DRB1*07 was found to be reduced in patients (9.8%) compared to both treated (35%: OR=0.18: 95% CI: 0.06-0.52: p=0.0011, pc=0.0154) and population controls (29%: OR=0.266: 95% CI: 0.11-0.65: 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 resistance 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.
authors.affiliation: Institute of Cellular Medicine, Newcastle University Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Donaldson
authors.forename: Ann K
authors.initials: AK
authors.lastname: Daly
authors.forename: Jill
authors.initials: J
authors.lastname: Henderson
authors.forename: Julia
authors.initials: J
authors.lastname: Graham
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: William
authors.initials: W
authors.lastname: Bernal
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
authors.forename: Guruprasad P
authors.initials: GP
authors.lastname: Aithal
mesh_terms: D000368:Aged; D000483:Alleles; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D019980:Amoxicillin-Potassium Clavulanate Combination