Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Microb Pathog. 2019 Mar;128:263-267. doi: 10.1016/j.micpath.2019.01.008. Epub 2019 Jan 10.
Hepatitis B virus (HBV) infection is a major public health concern due to the infection often leads to chronic infection, liver cirrhosis and also liver cancer. The host immune response to HBV infection and also genetic background play significant role in outcome of infection. Single nucleotide polymorphisms (SNPs) are the most important kind of variation in genetic sequences that caused by point mutations. As cytokines have major roles in viral infections, it seems that cytokine gene polymorphisms are independently associated with response to viral infections. Interleukin 21 (IL-21) plays an influential role in both innate and adaptive immune responses. Its specific receptor, IL-21R, produced and located on the surface of T, B and natural killer (NK) cells and is critical for the proliferation and differentiation of these immune effector cells. Many studies confirmed that the IL-21 involved in response to viral infections. We aimed to investigate the association of G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) gene polymorphisms with chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population.
In this study, blood samples were gathered from 320 patients with chronic HBV and 310 healthy controls and also 120 HBV spontaneous clearance individuals. Following genomic DNA extraction, genotypes of the selected SNPs determined by PCR and restriction fragment length polymorphism (RFLP) method. The results were analyzed by SPSS software using Chi-square, Logistic Regression, ANOVA and Independent Samples t-Test.
According to our results, in IL-21R (rs3093390 C/T) gene polymorphism, allele frequency of T is statistically different in the HBV spontaneous clearance group compared to chronic HBV cases. But there is no significant difference between G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) genotypes distribution in three groups. Also we found that higher serum aspartate transaminase (AST) level in HBV spontaneous clearance group is significantly associated with TT genotype of IL-21 (rs2055979) compared to GG genotype (P value = 0.006).
Our results showed that T allele frequency in IL-21R (rs3093390 C/T) gene polymorphism could consider as a host genetic factor for HBV spontaneous clearance. Probably we can serve it as a potential prognostic genetic marker for spontaneous clearance of HBV infection.
乙型肝炎病毒(HBV)感染是一个主要的公共卫生关注点,因为它通常会导致慢性感染、肝硬化,甚至肝癌。宿主对乙型肝炎病毒感染的免疫反应和遗传背景在感染的结果中起着重要作用。单核苷酸多态性(SNP)是遗传序列中最重要的变异类型,由点突变引起。由于细胞因子在病毒感染中起着重要作用,因此细胞因子基因多态性似乎与病毒感染的反应独立相关。白细胞介素 21(IL-21)在先天和适应性免疫反应中都起着重要作用。其特异性受体 IL-21R 在 T、B 和自然杀伤(NK)细胞上产生并位于其表面,对这些免疫效应细胞的增殖和分化至关重要。许多研究证实,IL-21 参与了对病毒感染的反应。我们旨在研究 G/T IL-21(rs2055979)和 C/T IL-21R(rs3093390)基因多态性与伊朗人群慢性乙型肝炎病毒感染和 HBV 自发清除之间的关系。
在这项研究中,从 320 名慢性 HBV 患者和 310 名健康对照者以及 120 名 HBV 自发清除者中采集了血液样本。提取基因组 DNA 后,通过聚合酶链反应和限制性片段长度多态性(RFLP)方法确定所选 SNP 的基因型。使用 SPSS 软件对结果进行分析,采用卡方检验、Logistic 回归、方差分析和独立样本 t 检验。
根据我们的结果,在 IL-21R(rs3093390 C/T)基因多态性中,与慢性 HBV 病例相比,HBV 自发清除组中 T 等位基因的频率在统计学上有所不同。但在三组中,G/T IL-21(rs2055979)和 C/T IL-21R(rs3093390)基因型分布没有显著差异。我们还发现,与 GG 基因型相比,HBV 自发清除组中较高的血清天冬氨酸转氨酶(AST)水平与 IL-21(rs2055979)的 TT 基因型显著相关(P 值=0.006)。
我们的结果表明,IL-21R(rs3093390 C/T)基因多态性中的 T 等位基因频率可作为乙型肝炎病毒自发清除的宿主遗传因素。我们可以将其作为 HBV 感染自发清除的潜在预后遗传标志物。