Z Gastroenterol 2007; 45 - A4_04
DOI: 10.1055/s-2007-967862

Increased IRF–1 gene expression in A allele carriers of the G–300A promoter polymorphism

P Aidery 1, G Ramadori 1, S Mihm 1
  • 1Abteilung Gastroenterologie und Endokrinologie, Georg-August-Universität, Göttingen

Aim: Interferon regulatory factor–1 (IRF–1) is a type I and type II interferon (IFN) inducible transcription factor which is involved in the transcriptional regulation of the IFN response. By applying in vitro assays, a single nucleotide polymorphism (SNP) at position –300 within the promoter region of the IRF–1 gene has been demonstrated to influence its transcriptional activity. Recently, we were able to report on an association of the G–300A IRF–1 genotype and the outcome of an HCV infection. Our present study aimed to investigate whether IRF–1 gene expression is related to G–300A IRF–1 genotype in healthy individuals and in patients with chronic hepatitis C. Methods: Genomic DNA from healthy individuals (n=11) and chronic hepatitis C patients (n=18) was genotyped at the respective position by allelic discrimination. Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMC) either directly after isolation or after an overnight incubation in the absence or presence of human recombinant IFN-α. IRF–1 and reference transcripts were quantified by TaqMan real time RT PCR. Results: For both, healthy volunteers and chronic hepatitis C patients, the amount of IRF–1 transcripts was not found to be associated with G–300A IRF–1 genotype distribution. Ex vivo basal IRF–1 gene expression, however, was significantly higher in chronic hepatitis C patients compared to healthy volunteers. Moreover, an overnight incubation led to an increase in IRF–1 transcripts preferentially in A allele carriers, whereas such an increase was not observed for healthy individuals nor for chronic hepatitis C patients homozygous for the wildtype allele G. Incubation of PBMCs with IFN-α led to an only marginal increase of IRF–1 mRNA in chronic hepatitis C patients (1.3-fold) independently on their IRF–1 genotpye compared to a mean 3.4-fold increase in the healthy group. Conclusion: Basal levels of IRF–1 transcripts seem not to differ with respect to G–300A IRF–1 genotype both in healthy individuals and in chronic hepatitis patients. Under certain conditions, however, i.e. an overnight incubation with autologous HCV containing sera, carriers of the variant allele A show a markedly higher IRF–1 mRNA expression than those who are homozygous for the G allele, whereas stimulation with IFN-α has a comparatively marginal genotype-independent effect. ASTQ studies are running to evaluate the functional impact of the two alleles.