Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China.
Department of Infectious Disease and Hepatic Disease, First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Front Cell Infect Microbiol. 2023 May 24;13:1180366. doi: 10.3389/fcimb.2023.1180366. eCollection 2023.
Hepatitis B virus (HBV) infection causes serious liver diseases and is a healthy problem worldwide. Although vaccines are administered to infants after birth, there is no effective medicine for HBV infection. The interferon-stimulated genes (ISGs) are important factors in the host that can aid in restraining the virus, and the gene has a wide-antiviral spectrum.
In this study, three SNPs in the gene were sequenced and genotyped, and their potential function were predicted and further verified by dual-luciferase reporter assay.
Although no significant difference of genotype and allele frequency was observed between HBV patients and the controls, the genotype and allele frequency showed significant difference between HBV patients with HBsAg-positive and HBV patients with HBsAg-negative or controls. Genotype AA (= 0.009) and AT (= 0.019) of rs77076061 showed higher and lower frequency in HBV patients with HBsAg-positive than in patients with HBsAg-negative, respectively. Genotype AG of rs1979262 played a risk role in HBV patients with HBsAg-positive (13.22%) than in patients with HBsAg-negative (7.53%, = 0.036) or controls (8.48%, = 0.033). The frequency of allele A of rs1979262 was higher in patients with HBsAg-positive (6.61%) than in patients with HBsAg-negative (3.77%, = 0.042), while it was the opposite for the allele G. Moreover, the associations between genotypes of SNPs in the gene and the ALT, AST, and DBIL level were also identified. The functional assay suggested that the SNPs might influence the expression by changing the connection of transcriptional factors.
In summary, the association between genetic polymorphisms in the gene and HBV infection/biochemical indices of patients was firstly identified in Yunnan Province.
乙型肝炎病毒(HBV)感染可导致严重的肝脏疾病,是一个全球性的健康问题。尽管婴儿出生后会接种疫苗,但目前尚无针对 HBV 感染的有效药物。干扰素刺激基因(ISGs)是宿主中重要的抗病毒因子,而基因具有广泛的抗病毒谱。
本研究对基因中的三个 SNP 进行了测序和基因分型,并通过双荧光素酶报告基因检测对其潜在功能进行了预测和进一步验证。
虽然 HBV 患者与对照组之间基因型和等位基因频率无显著差异,但 HBsAg 阳性的 HBV 患者与 HBsAg 阴性或对照组之间的基因型和等位基因频率存在显著差异。与 HBsAg 阴性患者相比,rs77076061 的基因型 AA(=0.009)和 AT(=0.019)在 HBsAg 阳性的 HBV 患者中频率更高,而 rs1979262 的基因型 AG 在 HBsAg 阳性的 HBV 患者中扮演着风险角色(13.22%),而在 HBsAg 阴性患者中(7.53%,=0.036)或对照组中(8.48%,=0.033)则较低。rs1979262 的等位基因 A 在 HBsAg 阳性患者中的频率(6.61%)高于 HBsAg 阴性患者(3.77%,=0.042),而等位基因 G 则相反。此外,还鉴定了基因中 SNP 的基因型与 ALT、AST 和 DBIL 水平之间的相关性。功能分析表明,这些 SNP 可能通过改变转录因子的结合方式影响的表达。
综上所述,首次在云南省发现基因多态性与 HBV 感染/患者生化指标之间存在关联。