雌激素受体α(ESR1)基因PvuⅡ和XbaⅠ位点基因多态性与HBV慢性感染的相关性研究

Association of PvuⅡand XbaⅠ Polymorphisms in Estrogen Receptor alpha(ESR1) Gene with the Chronic Hepatitis B Virus Infection

目的:探讨雌激素受体ESR1(Estrogen Receptor alpha gene)基因的PvuⅡ(rs2234693)和XbaⅠ (rs9340799)两个单核苷酸多态性(single nucleotide polymorphisms, SNPs)位点的基因多态性与乙型肝炎病毒HBV(Hepatitis B Virus)慢性感染的相关性,为控制HBV持续感染提供新的思路和科学依据。方法:选择107例慢性乙型病毒性肝炎患者为病例组及107例同期体检的健康人群为对照组,基于高分辨熔解曲线技术(High Resolution Melting,HRM)建立PCR-HRM分子诊断方法,检测其雌激素受体ESR1基因两个SNP位点rs2234693(T>C)和rs9340799(A>G)的基因多态性,并通过基因测序进一步验证,探讨上述两个SNP位点与HBV慢性感染的相关性。结果:病例组和健康对照组ESR1基因rs2234693(T>C)位点的基因型频率比较差异具有统计学意义(P<0.05),而两组间rs2234693位点等位基因频率比较差异没有统计学意义(P>0.05);病例组和健康对照组间ESR1基因rs9340799(A>G)位点的各基因型频率差异具有统计学意义(P<0.05),慢性乙肝病例组GG基因型明显升高,两组间rs9340799位点等位基因频率差异亦具有统计学意义(P<0.05)。Logistic回归分析显示rs9340799位点的G基因可增加HBV慢性感染的发病风险,A基因可降低HBV慢性感染的发病风险。结论:雌激素受体基因ESR1的rs9340799 (A>G)位点的GG基因型和G等位基因可能是HBV感染慢性化的遗传易感基因,GG基因型与HBV的慢性感染具有一定的相关性。

Objective: To investigate the correlation of PvuⅡ(rs2234693) and XbaⅠ(rs9340799) polymorphisms in estrogen Receptor alpha(ESR1) gene with Chronic Hepatitis B Virus Infection, and provide new ideas and scientific basis for controlling chronic infection of HBV. Methods: The molecular diagnosis methods of PCR-HRM bsaed on the high resolution melting curve technique(HRM) were established, 107 patients with chronic hepatitis B(CHB) and 105 healthy controls were selected, the gene polymorphisms of two SNPs were determined by PCR-HRM. The results were further verified by gel electrophoresis and gene sequencing, the correlation between these two SNP sites and HBV chronic were analyzed. Results: The genotype frequencies of rs2234693 site were significantly different between CHB cases and the controls(P<0.05), the allele frequency of rs2234693 showed no difference between two groups. The genotype frequencies of rs9340799 site was significantly different between CHB cases and the controls(P<0.05). The GG genotype was significantly increased in the chronic hepatitis B group. The allele frequency of rs9340799 site was significantly different between the two groups(P<0.05). According to Logistic regression analysis, the G gene of rs9340799 could increase the risk of chronic infection of HBV and the A gene could reduce the risk of chronic infection of HBV. Conclusions: The GG genotype and G allele of rs9340799(A>G) of estrogen-receptor gene ESR1 may be the genetic susceptibility gene of HBV infection. The GG genotype is associated with chronic infection of HBV.