Alborzi Abdolvahab, Hashempour Tayebeh, Moayedi Javad, Musavi Zahra, Pouladfar Gholamreza, Merat Shahin
Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Med Microbiol Immunol. 2017 Apr;206(2):165-174. doi: 10.1007/s00430-017-0497-y. Epub 2017 Feb 18.
Interleukin-28B (IL-28B) is suspected to be associated with response to treatment and one of the basic immunological backgrounds in liver transplant candidate (LTC). We aimed to assess whether genotypes of IL-28B can play a role in therapeutic response or advanced stages of liver disease. A total of 364 subjects were genotyped for IL-28B rs12979860 and rs8099917 SNPs using PCR-RFLP assay. Moreover, IL-28 serum level, HCV loads, and genotype were performed. A significant increase was observed in the frequencies of unfavorable rs12979860 genotypes/CT + TT in the chronic hepatitis C (CHC) and LTC groups. In the case of rs8099917, CHC group had a significantly higher frequency of unfavorable genotypes/GT + GG compared to the healthy group. IL-28B serum level was also significantly higher in healthy group compared with the CHC and LTC groups. There were no differences in the distribution of the IL-28B genotypes and haplotypes between responder and non-responder patients. Our results suggest, for the first time, that unfavorable rs12979860 genotypes can be considered one of the important immunological backgrounds in the Iranian LTC population that was confirmed with the lower IL-28 serum level compared to healthy group. Besides, there was a possible association of favorable IL-28B genotypes with lower odds of susceptibility to CHC infection but no support for a positive association between analyzed SNPs and an outcome of therapy. Moreover, non-CT haplotypes may be regarded as a genetic risk factor that can increase the chance of infection with HCV and progression toward end-stage HCV-related liver disease.
白细胞介素-28B（IL-28B）被怀疑与治疗反应以及肝移植候选者（LTC）的基本免疫背景之一有关。我们旨在评估IL-28B的基因型是否会在治疗反应或肝病晚期中发挥作用。使用PCR-RFLP分析法对总共364名受试者的IL-28B rs12979860和rs8099917单核苷酸多态性进行基因分型。此外，还检测了IL-28血清水平、丙型肝炎病毒（HCV）载量和基因型。在慢性丙型肝炎（CHC）组和LTC组中，不利的rs12979860基因型/CT + TT的频率显著增加。就rs8099917而言，与健康组相比，CHC组中不利基因型/GT + GG的频率显著更高。健康组的IL-28B血清水平也显著高于CHC组和LTC组。在有反应者和无反应者患者之间，IL-28B基因型和单倍型的分布没有差异。我们的结果首次表明，不利的rs12979860基因型可被视为伊朗LTC人群重要的免疫背景之一，这一点通过与健康组相比更低的IL-28血清水平得到证实。此外，有利的IL-28B基因型可能与较低的CHC感染易感性相关，但所分析的单核苷酸多态性与治疗结果之间没有正向关联的证据。此外，非CT单倍型可能被视为一种遗传风险因素，它会增加感染HCV以及发展为终末期HCV相关肝病的几率。
