title: HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease.
abstract: Drug-induced idiosyncratic liver disease (DIILD) depends largely on host susceptibility factors. Small studies support the genetic influence of human leukocyte antigen (HLA) class II molecules on the predisposition to DIILD. We sought associations between HLA-DRB and -DQB alleles and DIILD considered collectively or according to the biochemical expression of liver damage. We studied a total of 140 patients with a definitive or probable diagnosis of DIILD, as assessed with the Council for International Organizations of Medical Sciences scale, with 635 volunteer bone marrow and blood donors serving as controls. HLA-DRB1* and -DQB1* genotyping was performed by hybridization with sequence-specific oligonucleotides after genomic amplification. The group with DIILD did not differ from control subjects with regard to the distribution of HLA-DRB and -DQB antigens. The frequencies of alleles DRB1*15 (35.4% vs. 18.6% of controls; P =.002; odds ratio [OR] 2.31) and DQB1*06 (61.5% vs. 40.8%; P =.001; OR 2.32) were significantly increased in patients with the cholestatic/mixed type of liver damage in comparison to healthy subjects. By contrast, frequencies of alleles DRB1*07 (16.9% vs. 35.4%; P =.003; OR 0.37) and DQB1*02 (32.3% vs. 55.8%; P =.0003; OR 0.39) were significantly decreased. In conclusion, there is no association between any specific HLA allele and the propensity to develop DIILD. However, the genetic influence associated with HLA class II alleles appears to play a role in the biochemical expression of liver injury in cholestatic/mixed hepatotoxicity and may explain why a given drug may cause different patterns of liver damage.
authors.affiliation: Unidad de Hepatología, Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Center, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos, Malaga, Spain. andrade@uma.es
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
authors.forename: Anabel
authors.initials: A
authors.lastname: Alonso
authors.forename: Miren
authors.initials: M
authors.lastname: García-Cortes
authors.forename: Elena
authors.initials: E
authors.lastname: García-Ruiz
authors.forename: Rafael
authors.initials: R
authors.lastname: Benitez
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Fernández
authors.forename: Gloria
authors.initials: G
authors.lastname: Pelaez
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero
authors.forename: Raquel
authors.initials: R
authors.lastname: Corpas
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Durán
authors.forename: Manuel
authors.initials: M
authors.lastname: Jiménez
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.forename: Flor
authors.initials: F
authors.lastname: Nogueras
authors.forename: Rafael
authors.initials: R
authors.lastname: Martín-Vivaldi
authors.forename: José María
authors.initials: JM
authors.lastname: Navarro
authors.forename: Javier
authors.initials: J
authors.lastname: Salmerón
authors.forename: Felipe Sánchez
authors.initials: FS
authors.lastname: de la Cuesta
authors.forename: Ramón
authors.initials: R
authors.lastname: Hidalgo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; 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
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains