Youssef Samar S, Hamdy Nadia M
Genetic Engineering Division, Microbial Biotechnology Department, National Research Centre, El Behous st, Dokki, Cairo, Giza, 12311, Egypt.
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo, 11566, Egypt.
Arch Virol. 2017 Nov;162(11):3347-3354. doi: 10.1007/s00705-017-3498-7. Epub 2017 Jul 31.
In this paper we explore the role of suppressor of cytokine signaling 1 (SOCS1) (rs243327), the regulator of toll-like receptor-9 (TLR9) (rs352140), retinoic acid inducible gene-I (RIG-I) (rs669260), and cluster of differentiation 152 (CD152) (rs231776) in fibrotic/cirrhotic patients. Single nucleotide polymorphisms (SNPs) within these genes as well as haplotype analyses were performed on a cohort of 120 Egyptian fibrotic patients. Fibrosis had progressed from HCV genotype 4 infections. Using RT-PCR, SNPs were evaluated in the DNA collected from each patient using TaqMan genotyping assays. A regression model was used to evaluate allelic and haplotypic associations with a fibrosis/cirrhotic scale. The necroinflammatory A score was adjusted for non-genetic covariates. The genotype distributions for SOCS1 (rs243327) and TLR-9 (rs352140) differed significantly between the F1-F3 and F3-F4 groups. On the other hand, the genotype distributions for RIG-I (rs669260) and CD152 (rs231776) genes did not significantly differ. The allele frequency was calculated using Hardy-Weinberg Equilibrium (HWE) for the SOCS1 (rs243327), RIG-I (rs669260), and CD152 (rs231776) genes. These calculated frequency values indicated the need to compare them to another population for that locus. However, TLR9 (rs352140) did not show similar results. The A allele in SOCS1, TLR9, and RIG-I SNPs was an adverse prognostic factor for liver fibrosis and liver activity. Haplotype analysis revealed a significant association between SOCS1 and TLR9 in fibrotic/cirrhotic patients. This indicated the presence of the A allele in either gene, which is considered a risk factor for the progression of liver disease to cirrhosis. SOCS1 rs243327, TLR9 rs352140, and RIG-I rs669260 polymorphisms might affect liver pathophysiology and the cirrhotic outcome following genotype 4 HCV infection. Therefore, performing this specific SNP testing may be of value for the stratification of the population at risk.
在本文中，我们探讨了细胞因子信号转导抑制因子1（SOCS1）（rs243327）、Toll样受体9（TLR9）调节因子（rs352140）、维甲酸诱导基因I（RIG-I）（rs669260）以及分化簇152（CD152）（rs231776）在纤维化/肝硬化患者中的作用。对120例埃及纤维化患者进行了这些基因内的单核苷酸多态性（SNP）以及单倍型分析。纤维化由丙型肝炎病毒4型感染进展而来。使用逆转录聚合酶链反应（RT-PCR），通过TaqMan基因分型检测对从每位患者收集的DNA中的SNP进行评估。使用回归模型评估等位基因和单倍型与纤维化/肝硬化分级的关联。针对非遗传协变量对坏死性炎症A评分进行了调整。F1 - F3组和F3 - F4组之间，SOCS1（rs243327）和TLR - 9（rs352140）的基因型分布存在显著差异。另一方面，RIG-I（rs669260）和CD152（rs231776）基因的基因型分布没有显著差异。使用哈迪-温伯格平衡（HWE）计算了SOCS1（rs243327）、RIG-I（rs669260）和CD152（rs231776）基因的等位基因频率。这些计算出的频率值表明需要将其与该位点的另一人群进行比较。然而，TLR九（rs352140）并未显示出类似结果。SOCS1、TLR9和RIG-I SNP中的A等位基因是肝纤维化和肝脏活性的不良预后因素。单倍型分析显示，在纤维化/肝硬化患者中，SOCS1和TLR9之间存在显著关联。这表明任一基因中存在A等位基因，这被认为是肝病进展为肝硬化的危险因素。SOCS1 rs243327、TLR9 rs352140和RIG-I rs669260多态性可能会影响4型丙型肝炎病毒感染后的肝脏病理生理学和肝硬化结局。因此，进行这种特定的SNP检测可能对高危人群的分层有价值。
