BACKGROUND/AIMS: 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.
BACKGROUND/AIMS: 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: William R Proctor; Mala Chakraborty; Lynette S Chea; Jeffrey C Morrison; Julia D Berkson; Kenrick Semple; Mohammed Bourdi; Lance R Pohl Journal: Hepatology Date: 2013-03-15 Impact factor: 17.425
Authors: Ann K Daly; Peter T Donaldson; Pallav Bhatnagar; Yufeng Shen; Itsik Pe'er; Aris Floratos; Mark J Daly; David B Goldstein; Sally John; Matthew R Nelson; Julia Graham; B Kevin Park; John F Dillon; William Bernal; Heather J Cordell; Munir Pirmohamed; Guruprasad P Aithal; Christopher P Day Journal: Nat Genet Date: 2009-05-31 Impact factor: 38.330