中国汉族人群APOB rs10199768和rs1367117基因多态性与HBeAg阳性慢性乙型肝炎患者PEG-IFN-α疗效的相关性

Correlation between APOB rs10199768 and rs1367117 Gene Polymorphisms and PEG-IFN-αEfficacy in Patients with HBeAg-Positive Chronic Hepatitis B in Chinese Han Population

目的探讨中国汉族人群载脂蛋白B(APOB)rs10199768和rs1367117基因多态性与HBeAg阳性慢性乙型肝炎(CHB)患者聚乙二醇干扰素α(PEG-IFN-α)疗效的相关性。方法纳入124例PEG-IFN-α治疗的HBeAg阳性CHB患者,进行单核苷酸多态性(SNP)检测和临床指标分析,观察SNP与PEG-IFN-α疗效、临床指标变化的关系,以未经抗病毒治疗患者体外培养外周血单个核细胞(PBMC)为对象,探讨SNP与IFN-α效应的关系。结果APOB rs10199768和rs1367117的基因型在PEG-IFN-α完全应答(CR)组和应答不佳(SR)组之间的分布差别具有统计学意义(P=0.036和P=0.021);SR组中的rs10199768 CC基因型和C等位基因频率显著高于CR组(P=0.036,OR=3.844;P=0.040,OR=3.600);SR组中的rs1367117 GG基因型和G等位基因频率显著高于CR组(P=0.021,OR=2.647;P=0.017,OR=2.384)。在PEG-IFN-α治疗12和24周时,rs10199768 AC基因型患者的HBeAg浓度较CC型低(P=0.017;P=0.018)。IFN-α体外刺激实验显示,rs10199768 AA+AC型感染者的信号传导及转录活化因子1(STAT1)和干扰素刺激基因15(ISG15)的mRNA表达水平均较CC型高(P=0.005;P=0.018),但在rs1367117 GG/AG基因型中的表达差别均无统计学意义(P>0.05)。结论中国汉族人群APOB rs10199768和rs1367117基因多态性与PEG-IFN-α治疗HBeAg阳性CHB患者的疗效有关。rs10199768 A等位基因与PEG-IFN-α应答有关,rs1367117 G等位基因与PEG-IFN-α应答不佳有关。

Objective To investigate the association of apolipoprotein B(APOB)polymorphisms and the efficacy of pegylated interferon-α(PEG-IFN-α)in patients with HBeAg-positive chronic hepatitis B(CHB)in Chinese Han population.Methods A total of 124 HBeAg-positive CHB patients treated with PEG-IFN-αwere enrolled for single nucleotide polymorphism(SNP)detection and clinical index analysis to observe the relationship between SNP and PEG-IFN-αefficacy or clinical index.In vitro experiment of peripheral blood mononuclear cells(PBMC)from patients without antiviral therapy was performed for investigating the relationship between SNP and IFN-αefficacy.Results The distribution of APOB rs10199768 and rs1367117 genotypes were significantly different between PEG-IFN-αCR/SR groups(P=0.036 and P=0.021).The frequencies of CC genotype and C allele of rs10199768 in SR group were significantly higher than those in CR group(P=0.036,OR=3.844,and P=0.040,OR=3.600).The frequencies of rs1367117 GG genotype and G allele in SR group were significantly higher than those in CR group(P=0.021,OR=2.647,and P=0.017,OR=2.384).At week 12 and week 24 of PEG-IFN-αtreatment,the concentration of HBeAg in patients with rs10199768 AC genotype was lower than that with CC genotype(P=0.017 and P=0.018).In vitro IFN-αstimulation assay showed that the mRNA expression of signal transduction and transcriptional activator factor 1(STAT1)and interferon-stimulated genes 15(ISG15)were higher in patients with rs10199768 AA+AC genotype than those with CC genotype(P=0.005 and P=0.018),but there was no significant difference in rs1367117 GG/AG genotype(P>0.05).Conclusion There is correlations between polymorphisms of APOB rs10199768/rs1367117 and the efficacy of PEG-IFN-αmanagement in HBeAg-positive CHB patients in Chinese Han population.rs10199768 A allele may be related to PEG-IFN-αresponse,while rs1367117 G allele may be related to PEG-IFN-αsub-optimal response.