Objective: To investigate the association between single nucleotide polymorphisms (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through a large-sample control study, and to provide a basis for the development of individualized blocking strategies for pregnant women with a high viral load. Methods: The genotypes of rs3130542 and rs4821116 were determined for 312 pregnant women with a high viral load who received telbivudine antiviral therapy during the second or third trimester of pregnancy, and the dominant model, recessive model, and additive model were used to analyze the association between the genotypes of these two loci and the reduction in HBV DNA load. The Shapiro-Wilk test and the Levene test were used to evaluate data normality and homogeneity of variances, and the t-test or the non-parametric Mann-Whitney U test was selected based on data type and was used for the comparison of means between groups. The Hardy-Weinberg equilibrium was used to determine the genotype of SNPs, and the dominant model, recessive model, and additive model were used for analysis. Results: Mothers with an AA/AG genotype of rs3130542 in the HLA-C gene had a significantly higher probability of HBV DNA load ≥10(3) IU/ml at the time of delivery (P < 0.05) and a significantly higher risk of failure in the prevention of mother-to-child transmission, no matter whether they started to take telbivudine at week 24 or 28 of pregnancy. The association between the genotype of rs4821116 in the UBE2L3 gene and the reduction in viral load in pregnant women needed to be confirmed by studies with a larger sample size. Conclusion: Pregnant women with a high viral load and an AA/AG genotype of rs3130542 in the HLA-C gene tend to have poor response to antiviral therapy during pregnancy, and early antiviral intervention is recommended for such patients.
目的： 通过大样本、对照研究，探讨HBsAg阳性母亲HLA-C及UBE2L3基因rs3130542、rs4821116位点基因多态性与替比夫定孕期抗病毒效果的关系，为高病毒载量孕妇个体化阻断策略的制定提供依据。 方法： 检测312例孕中、晚期接受替比夫定抗病毒的高病毒载量孕妇rs3130542、rs4821116位点基因分型，通过显性模型、隐性模型和相加模型分析该位点基因型与母亲HBV DNA载量下降的关系。用Shapiro-Wilk和Levene检验评估数据正态性和方差齐性，据数据情况，采用t检验或非参数Mann-Whitney U检验比较组间均数差异。SNP基因分型分析中，进行哈迪-温伯格平衡检验，显性模型、隐性模型和相加模型分析。 结果： 无论孕24周还是孕28周开始用替比夫定治疗，母亲HLA-C基因rs3130542位点为AA/AG基因型时，HBV DNA载量至分娩前仍≥10(3) IU/ml的可能性更大（P < 0.05），发生母婴阻断失败的几率更高；UBE2L3基因rs4821116位点的基因分型与孕妇病毒下降的相关性需更大样本来证明。 结论： HLA-C基因rs3130542位点为AA/AG基因型的高病毒载量孕妇，孕期抗病毒干预效果相对不佳，更适合提早进行抗病毒干预。.
Keywords: Hepatitis B, chronic; Polymorphism, single nucleotide; Pregnant women; Telbivudine.