CFTR基因多态性与原发性肝内胆管结石发病风险的关系  

Association of primary intrahepatic lithiasis with the polymorphisms of the cystic fibrosis transmembrane conductance regulator gene

作　　者：梅璇 吴海聪 林静 郑娇龙 刘邦 李东良 MEI Xuan;WU Haicong;LIN Jing;ZHENG Jiaolong;LIU Bang;LI Dongliang(Department of Hepatobiliary Medicine,The 900th Hospital of PLA Joint Logistics Support Force&Fuzong Clinical Medical College of Fujian Medical University,Fuzhou 350025,China)

机构地区：[1]解放军联勤保障部队第九〇〇医院(福建医科大学福总临床医学院)肝胆内科,福州350025

出　　处：《临床肝胆病杂志》2021年第12期2878-2882,共5页Journal of Clinical Hepatology

基　　金：福建省社会发展科技引导项目(2016Y0068);福建医科大学启航基金(2017XQ1205)。

摘　　要：目的探讨中国汉族人群囊性纤维化跨膜转导调节因子(CFTR)基因常见的多态性位点与原发性肝内胆管结石(PIL)发病的相关性。方法选择2018年6月—2018年11月在解放军联勤保障部队第九〇〇医院就诊的PIL患者104例,以及同期120例健康体检者,采用一代测序法检测CFTR基因的M470V、TG-repeats、Poly-T位点等位基因和基因型,比较2组研究对象的年龄、性别构成比、发病年龄、等位基因及基因型频率,分析CFTR的3个多态性位点与PIL发病风险的相关性。用K-S检验判断连续变量的正态性。呈正态分布计量资料2组间比较用独立样本t检验,计数资料及等位基因及基因型频率比较、Hardy-Weinberg平衡采用χ^(2)检验进行分析。基因型、等位基因与疾病发生风险评估采用二元logistic回归分析。偏离Hardy-Weinberg平衡的位点与PIL发病风险相关性采用调整OR值(OR adj)表示。结果PIL组和对照组间的M470V位点上的等位基因(χ^(2)=15.139,P<0.01)和基因型(χ^(2)=22.889,P<0.01)在2组间差异有统计学意义。TG-repeat、Poly-T两位点上等位基因及个体基因型在2组间差异均无统计学意义(P值均>0.05)。PIL患者M470V位点上等位基因G频率明显高于对照组(60.10%vs 41.67%,P<0.01)。与AA基因型个体相比,GG(OR=4.680,P<0.01)、AG基因型(OR=2.500,P<0.01)个体发生PIL的风险显著升高。在TG-repeats位点,12TG/13TG基因型个体的PIL发病风险较11TG/12TG个体更高(OR=11.002,P=0.042);在Poly-T位点7T/5T基因型个体的PIL发病风险较7T/7T个体更低(OR=0.079,P=0.047)。结论中国汉族人群CFTR基因中M470V位点多态性与PIL发病风险独立相关,等位基因G是PIL发病的高危突变。Objective To investigate the association of common polymorphism loci of the cystic fibrosis transmembrane conductance regulator(CFTR)gene with the onset of primary intrahepatic lithiasis(PIL)in the Chinese Han population.Methods A total of 104 patients with PIL who attended The 900th Hospital of PLA Joint Logistics Support Force from June to November 2018 were enrolled as PIL group,and 120 healthy controls who underwent physical examination during the same period of time were enrolled as control group.Sanger sequencing was used to detect the alleles and genotypes at the M470V,TG-repeats,and Poly-T loci of the CFTR gene.The two groups were compared in terms of age,sex ratio,age of onset,and allele and genotype frequencies,and the association of the above three polymorphism loci of the CFTR gene with the risk of PIL was analyzed.The K-S test was used to determine the normality of continuous variables.The independent samples t-test was used for comparison of normally distributed continuous data between two groups,and the chi-square test was used to compare categorical data and allele/genotype frequencies and analyze Hardy-Weinberg equilibrium.A binary logistic regression analysis was used to investigate the association of genotypes and alleles with the risk of the disease.The association of the loci deviating from Hardy-Weinberg equilibrium with the risk of PIL was expressed as adjusted odds ratio(OR).Results There were significant differences between the PIL group and the control group in the distribution of alleles(χ^(2)=15.139,P<0.01)and genotypes(χ^(2)=22.889,P<0.01)at the M470V locus,while there were no significant differences between the two groups in the distribution of alleles and genotypes at the TG-repeats and Poly-T loci(all P>0.05).The PIL group had a significantly higher frequency of G allele at the M470V locus than the control group(60.1%vs 41.67%,P<0.01).Compared with the individuals with AA genotype,the individuals with GG and AG genotypes had a significant increase in the risk of PIL(OR=4.680 and

关 键 词：胆结石 胆管 肝内 多态现象 遗传 危险因素 

分 类 号：R657.42[医药卫生—外科学]