title: Analysis of IL-10, IL-4 and TNF-alpha polymorphisms in drug-induced liver injury (DILI) and its outcome.
abstract: OBJECTIVE
  The aim of this study was to assess whether genetic polymorphism of three important candidate cytokine genes, IL-10 (-1082G/A, -819C/T, and -592C/A), IL-4 (-590C/T) and TNF-alpha (-308G/A), play a role in the susceptibility to developing drug-induced liver injury (DILI), and in determining its phenotypic expression and severity.
  
  
  METHODS
  Cytokine genotyping was analysed using TaqMan 5' allelic discrimination assay in 140 DILI patients (mean age 51 y, range 13-82, with equal sex distribution) included in the Spanish Registry and 268 healthy controls.
  
  
  RESULTS
  Genotypes, haplotypes and allele frequencies were similar for both cases and controls. The low IL-10 producing haplotype was more prevalent in DILI patients with the absence of peripheral blood eosinophilia (Pc=0.004, OR=5.29, 95% CI: 2.04-13.67), revealing significantly lower median eosinophil counts (0.19 x 10(9)L; P<0.0002) compared to the intermediate (0.24 x 10(9)L) and high (0.40 x 10(9)L) IL-10 haplotypes. All cases with serious DILI outcome carried low or intermediate IL-10 producing haplotype and had normal or low eosinophil counts.
  
  
  CONCLUSIONS
  IL-10, IL-4 and TNF-alpha genetic polymorphisms were not related to the risk of developing DILI. Low IL-10 producing haplotype is associated with low eosinophil count, absence of eosinophilia and may be associated with worse clinical outcome from DILI.
authors.affiliation: Servicio de Farmacología Clínica, Facultad de Medicina, Departmento de Farmacología, Boulevard Louis Pasteur, 32, Campus de Teatinos s/n, 29071 Málaga, Spain.
authors.forename: Ketevan
authors.initials: K
authors.lastname: Pachkoria
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
authors.forename: Esperanza
authors.initials: E
authors.lastname: Crespo
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Cabello
authors.forename: Susana
authors.initials: S
authors.lastname: Lopez-Ortega
authors.forename: M A Carmen
authors.initials: MA
authors.lastname: Fernandez
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.forename: Ana
authors.initials: A
authors.lastname: Madrazo
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Durán
authors.forename: Ana Malcon
authors.initials: AM
authors.lastname: de Dios
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Borraz
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Navarro
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics*; D004804:Eosinophils / Q000166:cytology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D012042:Registries; D012307:Risk Factors; D012720:Severity of Illness Index; D013030:Spain / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; C508598:IL4 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4