ABCB11基因V444A突变与原发性肝胆管结石的相关性分析

Research on the relationship between V444A mutation of ABCB11 gene and primary intrahepatic stone

目的探讨ABCB11基因V444A突变与原发性肝胆管结石发生的相关性。方法采取病例对照研究方法选取联勤保障部队第九〇〇医院肝胆病中心2017年10月至2019年6月确诊的164例福建籍原发性肝胆管结石患者[男91例,女73例,年龄(46.0±13.0)岁]和164名同一地区健康对照人群[男99名,女65名,年龄(43.8±16.7)岁]为研究对象。采用TaqMan-MGB探针方法对ABCB11基因V444A SNPs多态性位点进行检测,计算上述位点等位基因和基因型频率,采用Pearsonχ2检验对所检出的等位基因及基因型进行关联分析;logistic回归分析各基因型与肝胆管结石患病相关性。结果两组人群年龄和性别比较差异均无统计学意义(均P>0.05);Hardy-Weinberg平衡检验结果显示对照组人群中V444A位点的基因型及等位基因频率符合Hardy-Weinberg遗传平衡定律,所选人群具有代表性(P=0.161);V444A位点等位基因及基因型共检出T、C 2个等位基因,TT、TC、CC 3个基因型,病例组中T、C等位基因频率分别为28.4%和71.6%,对照组中T、C等位基因频率分别为35.4%和64.6%,两组等位基因频率分布差异无统计学意义(P=0.054),病例组中TT、TC、CC的基因型频率为5.5%、45.7%、48.8%,对照组中TT、TC、CC的基因型频率为14.6%、41.5%、43.9%,两组基因型分布差异有统计学意义(P=0.023);V444A位点基因型与肝内胆管结石的发病风险的多因素分析发现该位点TC型杂合突变可能增加原发性肝内胆管结石的患病风险。结论ABCB11基因V444A突变可能是肝内胆管结石发病的一个危险因素。

Objective To investigate the relationship between V444A mutation of the ABCB11 gene and primary intrahepatic stone(PIS).Methods A total of 164 patients(including 91 males and 73 females,with an average age of(46.0±13.0)years)with PIS and 164 healthy(including 99 males and 65 females,with an average age of(43.8±16.7)years)volunteers were enrolled in this case-control study between October 2017 and June 2019.TaqMan-MGB was used for detecting the V444A polymorphism site of the ABCB11 gene.All the genotypes and allele frequencies were calculated.Pearson chi-squared test was performed to detect the differences in allele and genotype distribution between the two groups.Logistic regression analysis was used to identify genotypes associated with PIS.Results There was no significant difference in age and gender between the two groups(both P>0.05).The distributions of V444A allele and genotype accorded with Hardy-Weinberg equilibrium law(P=0.161),which indicated that the selected control group represented statistically acceptable sample.Two alleles of T and C,and three genotypes of TT,TC and CC were detected in the locus of V444A.The T and C allele frequencies in the PIS group and the control group were 28.4%vs 35.4%,and 71.6%vs 64.6%,respectively.The frequencies of the T and C alleles were not different between the two groups(P=0.054).The frequencies of TT,TC and CC genotypes in the two groups were 5.5%,45.7%,48.8%,and 14.6%,41.5%,43.9%,respectively,with significant difference between the two groups(P=0.023).Logistic regression analysis revealed the V444A polymorphism(TC heterozygous mutation)was associated with PIS.Conclusion ABCB11 gene polymorphism at the site of V444A may be related to the susceptibility of PIS.