■乙型肝炎病毒(HBV)感染会导致严重的肝脏疾病,并且是全球范围内的健康问题。尽管疫苗是在婴儿出生后接种的,目前尚无有效的HBV感染药物。干扰素刺激基因(ISGs)是宿主中有助于抑制病毒的重要因素,C19orf66基因具有广泛的抗病毒谱。
■在这项研究中,对C19orf66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测定对其潜在功能进行了预测和进一步验证。
■尽管HBV患者和对照组之间的基因型和等位基因频率没有显着差异,基因型和等位基因频率在HBsAg阳性的HBV患者和HBsAg阴性的HBV患者或对照之间显示出显着差异。rs77076061的基因型AA(P=0.009)和AT(P=0.019)在HBsAg阳性的HBV患者中显示出较高和较低的频率,分别。rs1979262基因型AG在HBsAg阳性的HBV患者(13.22%)比HBsAg阴性的患者(7.53%,P=0.036)或对照(8.48%,P=0.033)。rs1979262等位基因A的频率在HBsAg阳性患者(6.61%)高于HBsAg阴性患者(3.77%,P=0.042),而等位基因G则相反。此外,C19orf66基因中SNP的基因型与ALT之间的关联,AST,和DBIL水平也被鉴定。功能测定表明,SNP可能通过改变转录因子的连接来影响C19orf66的表达。
■总之,C19orf66基因多态性与HBV感染/生化指标的相关性在云南省首次被发现。
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 C19orf66 gene has a wide-antiviral spectrum.
In this study, three SNPs in the C19orf66 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 (P= 0.009) and AT (P= 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%, P= 0.036) or controls (8.48%, P= 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%, P= 0.042), while it was the opposite for the allele G. Moreover, the associations between genotypes of SNPs in the C19orf66 gene and the ALT, AST, and DBIL level were also identified. The functional assay suggested that the SNPs might influence the C19orf66 expression by changing the connection of transcriptional factors.
In summary, the association between genetic polymorphisms in the C19orf66 gene and HBV infection/biochemical indices of patients was firstly identified in Yunnan Province.