Mueller Tobias, Mas-Marques Andreas, Sarrazin Christoph, Wiese Manfred, Halangk Juliane, Witt Heiko, Ahlenstiel Golo, Spengler Ulrich, Goebel Uwe, Wiedenmann Bertram, Schreier Eckart, Berg Thomas
Charité, Campus Virchow-Klinikum, Medizinische Klinik mit Schwerpunkt, Hepatologie und Gastroenterologie, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
J Hepatol. 2004 Oct;41(4):652-8. doi: 10.1016/j.jhep.2004.06.021.
BACKGROUND/AIMS: Interleukin-12 (IL-12) governs the Th1-type immune response, affecting the spontaneous and treatment-induced recovery from HCV-infection. We investigated whether the IL12B polymorphisms within the promoter region (4 bp insertion/deletion) and the 3'-UTR (1188-A/C), which have been reported to influence IL-12 synthesis, are associated with the outcome of HCV infection.
We analyzed 186 individuals with spontaneous HCV clearance, 501 chronically HCV infected patients, and 217 healthy controls. IL12B 3'-UTR and promoter genotyping was performed by Taqman-based assays with allele-specific oligonucleotide probes and PCR-based allele-specific DNA-amplification, respectively.
The proportion of IL12B promoter and 3'-UTR genotypes did not differ significantly between the different cohorts. However, HCV genotype 1-infected patients with high baseline viremia carrying the IL12B 3'-UTR 1188-C-allele showed significantly higher sustained virologic response (SVR) rates (25.3% vs. 46% vs. 54.5% for A/A, A/C and C/C) due to reduced relapse rates (24.2% vs. 12% vs. zero % for A/A, A/C and C/C).
IL12B 3'-UTR 1188-C-allele carriers appear to be capable of responding more efficiently to antiviral combination therapy as a consequence of a reduced relapse rate. No association of IL12B polymorphisms and self-limited HCV infection could be demonstrated.
背景/目的：白细胞介素-12（IL-12）调控Th1型免疫反应，影响丙型肝炎病毒（HCV）感染的自发恢复及治疗诱导恢复。我们研究了据报道会影响IL-12合成的启动子区域（4bp插入/缺失）和3'-非翻译区（1188-A/C）内的IL12B多态性是否与HCV感染的结局相关。
我们分析了186例HCV自发清除者、501例慢性HCV感染者和217例健康对照。分别采用基于Taqman的等位基因特异性寡核苷酸探针法和基于PCR的等位基因特异性DNA扩增法进行IL12B 3'-非翻译区和启动子基因分型。
不同队列中IL12B启动子和3'-非翻译区基因型的比例无显著差异。然而，携带IL12B 3'-非翻译区1188-C等位基因的高基线病毒血症的HCV 1型感染患者，由于复发率降低（A/A、A/C和C/C分别为24.2%、12%和0%），其持续病毒学应答（SVR）率显著更高（A/A、A/C和C/C分别为25.3%、46%和54.5%）。
由于复发率降低，IL12B 3'-非翻译区1188-C等位基因携带者似乎能够更有效地对抗病毒联合治疗作出反应。未证实IL12B多态性与自限性HCV感染有关。
