CD40⁃rs1883832、CD40⁃rs4810485基因多态性与乙肝肝硬化遗传易感性及预后的关系

Relationship between genetic polymorphism of CD40⁃rs1883832 and CD40⁃rs4810485 and genetic suscepti⁃bility and prognosis of hepatitis B cirrhosis

目的探讨CD40⁃rs1883832、CD40⁃rs4810485基因多态性与乙肝肝硬化遗传易感性及预后的关系。方法选取2015年2月至2018年1月本院收治的480乙肝肝硬化患者、480例乙肝病毒感染者及480例健康体检者,分别设为病例组、乙肝组和健康组。采用聚合酶链反应⁃限制性片段长度多态性(PCR⁃RFLP)法分析CD40⁃rs1883832、CD40⁃rs4810485基因多态性,对比3组两位点基因型分布和等位基因频率,随访病例组患者2年生存情况,采用Cox回归分析法分析CD40⁃rs1883832、CD40⁃rs4810485基因多态性对乙肝肝硬化患者预后的影响;采用Kaplan⁃Meier法分析两位点不同基因型患者生存情况,并进行Log⁃rank检验。结果病例组CD40⁃rs1883832 T等位基因频率高于健康组和乙肝组,且乙肝组高于健康组(P<0.05);3组CD40⁃rs4810485 G等位基因频率比较,差异无统计学意义(P>0.05)。Cox回归分析显示,CD40⁃rs1883832位点CT、TT基因型是影响乙肝肝硬化预后的独立危险因素(HR=1.682、2.588,P<0.05);CD40⁃rs4810485基因位点CG、GG基因型与乙肝肝硬化预后无明显相关性(P>0.05)。480例乙肝肝硬化患者2年死亡率16.55%(72/145),其中CD40⁃rs1883832基因携带C等位基因(CC+CT)患者死亡33例,非携带C等位基因(TT)患者死亡39例,经Kaplan⁃Meier生存曲线分析,CC+CT基因型患者与TT基因型患者生存曲线比较,差异有统计学意义(P<0.05);CD40⁃rs4810485基因携带C等位基因(CC+CG)患者死亡51例,非携带C等位基因(GG)患者死亡21例,经Kaplan⁃Meier生存曲线分析,CC+CG基因型患者与GG基因型患者生存曲线比较,差异无统计学意义(P>0.05)。结论CD40⁃rs1883832基因多态性与乙肝肝硬化遗传易感性及预后关系密切,且与CC+CT基因型相比,TT基因型乙肝肝硬化患者预后不良风险更高。

Objective To explore the relationship between CD40⁃rs1883832 and CD40⁃rs4810485 gene polymorphisms and the genetic susceptibility and prognosis of hepatitis B cirrhosis.Methods 480 patients with hepatitis B cirrhosis,480 patients with hepatitis B virus and 480 healthy medical examiners admitted to our hospital from February 2015 to January 2018 were selected as case group,hepatitis B group and healthy group,respectively.The polymorphisms of CD40⁃rs1883832 and CD40⁃rs4810485 were analyzed by polymerase chain reaction⁃restric⁃tion fragment length polymorphism(PCR⁃RFLP)method,and the genotype distribution and allele frequency of the two loci were compared of the 3 groups.Follow⁃up the 2⁃year survival of the patients in the case group,the Cox regression analysis method was used to analyze the effect of CD40⁃rs1883832 and CD40⁃rs4810485 gene polymor⁃phisms on the prognosis of patients with hepatitis B cirrhosis.The Kaplan⁃Meier method was used to analyze the survival of two patients with different genotypes,and log⁃rank test was performed.Results The frequency of CD40⁃rs1883832 T allele in the case group was higher than that in the healthy group and hepatitis B group,and the hepa⁃titis B group was higher than the healthy group(P<0.05).There was no significant difference in the frequency of CD40⁃rs4810485 G allele between the 3 groups(P>0.05).Cox regression analysis showed that the CT and TT genotypes of CD40⁃rs1883832 were independent risk factors affecting the prognosis of hepatitis B cirrhosis(HR=1.682,2.588,P<0.05).The CG and GG genotypes of CD40⁃rs4810485 gene locus had no significant correlation with the prognosis of hepatitis B cirrhosis(P>0.05).The two⁃year mortality rate of 480 patients with hepatitis B cirrhosis was 16.55%(72/145).Among them,thirty⁃three patients with CD40⁃rs1883832 gene carrying C allele(CC+CT)died,and patients without C allele(TT)died 39 cases.According to Kaplan⁃Meier survival curve anal⁃ysis,the difference between the 2⁃year survival curves of patients with CC+CT genotype and TT genotype was statistically significant(P<0.05).Fifty⁃one patients with CD40⁃rs4810485 gene carrying C allele(CC+CG)died,and patients without C allele(GG)died 21 cases..According to Kaplan⁃Meier survival curve analysis,there was no statistically significant difference between the CC+CG genotype patient and the GG genotype patient 2⁃year survival curve(P>0.05).Conclusion The CD40⁃rs1883832 gene polymorphism is closely related to the genetic susceptibility and prognosis of hepatitis B cirrhosis,and compared with the CC+CT genotype,patients with TT genotype hepatitis B cirrhosis have a higher risk of poor prognosis.