维生素D受体基因TaqⅠ、FokⅠ单核苷酸多态与HBV感染结局关联探讨

Association of TaqⅠT/C and FokⅠC/T polymorphisms of vitamin D receptor gene with outcome of hepatitis B virus infection

目的探讨维生素D受体(VDR)基因TaqⅠT／C和FokⅠC／T多态性是否与HBV感染结局之间存在关联。方法采用病例-对照研究方法,募集212例HBV自限性感染者、244例无症状HBsAg携带者和391例慢性乙型肝炎患者作为研究对象,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对VDR基因TaqⅠ和FokⅠ基因进行分型测定。结果慢性乙肝组VDR-FokⅠC等位基因频率为45．8％,显著高于自限性感染组的38．2％(X2=6．43,P=0．01)。慢性乙型肝炎组VDR-FokⅠ的TT、TC及CC基因型频率分别为30．7％、47．1％和22．2％,与自限性感染组的基因型频率41．0％、41．5％和17．5％相比差异有统计学意义(X2=6．76,P=0．03)。单因素分析显示,携带CC／CT基因型的个体感染HBV后,增加发生慢性乙型肝炎的风险(OR=1．57,P=0．01),经Logistic回归分析,控制性别的混杂作用后,携带FokⅠCC／CT基因型者发生慢性乙肝的风险是TT基因型携带者的1．7倍(OR=1．70,P=0．021)。未发现VDR-TaqⅠT／C多态性与HBV感染结局存在显著关联。单体型分析显示,TaqⅠT-Fok C在慢性乙型肝炎组的频率为2．3080％,显著高于HBV自限性感染组的0．5391％(X2=6．08,P=0．01);TaqⅠT-FokⅠT在慢性乙型肝炎组的频率为1．5283％,显著低于HBV自限性感染组的3．7061％(X2=5．65,P=0．02)和显著低于HBV携带组的3．4820％(X2=5．12,P=0．02)。结论VDR基因多态性可能是影响HBV感染结局的因素之一。

Objective To determine whether TaqⅠ T/C and FokⅠ C/T polymorphisms of Vitamin D Receptor （VDR） gene was associated with the outcomes of hepatitis B virus （HBV） infection. Methods A total of 212 HBV self-limited infection individuals, 244 asymptomatic HBsAg carriers and 391 chronic hepatitis B （HB） patients were recruited to conduct a case-control study. VDR-TaqⅠ T/C and VDR-FokⅠ C/T polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results The frequency of VDR-FokⅠ allele C in the chronic HB patients was 45. 8%, significantly higher than 38.2% of the self-limited infection individuals （ X^2 = 6.43, P = 0.01 ）. The frequencies of VDR-FokⅠ genotypes TF, TC, and CC in HB patients were 30. 7%, 47.1%, and 22. 2% respectively, and 41.0% （ TT）, 41.5 % （ TC）, and 17.5 % （CC） in the self-limited infection individuals. There was a statistically significant difference between HB patients and self-limited infection individuals （X^2 = 6. 76,P = 0. 03）. The results of univariate analysis showed that the subjects canting VDR-FokⅠ CC / TC genotype had 1.57-fold elevated risk for developing chronic HB when they were infected HBV （ OR = 1.57 ,P =0. 01 ）. A multiple logistic regression analysis revealed that VDR-FokⅠ CC/CT was independently associated with chronic HB after adjusting both potential confounding effects of gender （ OR = 1.70, P =0. 021）. The statistically significant association between Taq I T/C polymorphism and outcome of HBV infection was not demonstrated in the study. The frequency of haplotype TC of VDR-TaqⅠ and FokⅠ in HB patients was 2. 3080%, significantly higher than O. 5391% of the self-limited infection individuals （ X^2 = 6. 08, P =0. 01）. However, the frequency of haplotype TT in the HB patients was 1. 5283%, significantly lower than 3. 7061% of the self-limited infection individuals （ X^2 = 5.65, P = 0. 02） and 3. 4820% of the HBV carriers （X^2 = 5. 12, P = 0. 02 ）. Conclusion VDR gene polymorphism is probably an influence factor on the genetic susceptibilitv of HBV infaction.