ABCG2基因启动子区rs2231142位点单核苷酸多态性与新疆维吾尔自治区汉族男性人群高尿酸血症易感性分析  

Single Nucleotide Polymorphism at the rs2231142 Locus of the ABCG2 Gene and Susceptibility to Hyperuricemia in the Population of Han Chinese Men in Xinjiang

作　　者：夏依代·图尔荪 何爽 孙红光 刘璐 叶飞 陈昱名 王宇婷 苗蕾[1] Xiayidai·Tuersun;HE Shuang;SUN Hongguang(School of Public Health,Xinjiang Medical University,Xinjiang 830011,China)

机构地区：[1]新疆医科大学公共卫生学院,乌鲁木齐830011 [2]新疆医科大学第一附属医院医学整形美容中心,乌鲁木齐830011 [3]新疆生产建设兵团疾控中心慢病科,乌鲁木齐830011

出　　处：《医学研究杂志》2024年第5期32-37,共6页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81460153)。

摘　　要：目的探讨ABCG2基因rs2231142(G/T)位点单核苷酸多态性与高尿酸血症易感性的关系。方法以2018~2020年在新疆医科大学附属中医医院、新疆维吾尔自治区人民医院、新疆医科大学第一附属医院就诊的865例男性为研究对象,收集其血液样本,按其血尿酸水平分为高尿酸血症组(n=367)和健康对照组(n=498)。采用多重荧光聚合酶链反应(polymerase chain reaction,PCR)技术检测ABCG2基因rs2231142(G/T)位点的基因型并观察两组的基因多态性。利用双荧光素酶报告基因实验证实该序列对荧光素酶表达活性的影响。结果高尿酸血症组的尿酸、体重指数、葡萄糖、肌酐、甘油三酯、舒张压、高密度脂蛋白、低密度脂蛋白高于健康对照组,差异均有统计学意义(P<0.05)。两组基因rs2231142位点均符合Hardy-Weinberg平衡性检验(P>0.05),表明该位点具有群体代表性。高尿酸血症组和健康对照组中GG、GT、TT 3种基因型的分布频率差异有统计学意义(χ^(2)=17.146,P<0.001),等位基因G和T在两组间分布频率比较差异有统计学意义(χ^(2)=19.115,P<0.001)。不同遗传模型中,TT基因型均表现为高尿酸血症的危险因素(加性模型OR=2.302,95%CI:1.472~3.603;显性模型OR=1.689,95%CI:1.283~2.210;隐性模型OR=1.867,95%CI:1.221~2.874)。尿酸、葡萄糖、甘油三酯在不同基因型分组间比较,差异均有统计学意义(P<0.05)。两两比较结果显示,G/T组与G/G组、T/T组与G/G组组间的尿酸、葡萄糖、甘油三酯水平差异均有统计学意义(P<0.05)。其中T/T组尿酸水平最高,G/G组葡萄糖和甘油三酯水平最高。双荧光素酶活性测定结果显示,rs2231142(G/T)具有启动子功能;且含G等位基因比含T等位基因的重组质粒荧光素酶报告基因的表达水平较高,是其1.120倍(P=0.012)。结论ABCG2基因rs2231142(G/T)位点单核苷酸多态性与高尿酸血症易感性间存在关联,等位基因T可能是高尿酸血症的危险因素。Objective To explore the relationship between single nucleotide polymorphisms at the rs2231142(G/T)locus of the ABCG2 gene and susceptibility to hyperuricemia.Methods A total of 865 male study subjects were collected from the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University,the People′s Hospital of Xinjiang Uygur Autonomous Region,and the First Affiliated Hospital of Xinjiang Medical University and other hospitals from 2018 to 2020,their blood samples were collected,and they were divided into hyperuricemia group(n=367)and healthy control group(n=498)according to blood uric acid levels.Multiplex fluorescent polymerase chain reaction(PCR)was used to detect the genotype of the rs2231142(G/T)locus of the ABCG2gene and to observe the gene polymorphism in the two groups.The effect of this sequence on luciferase expression activity was confirmed by dual luciferase reporter gene experiment.Results The values of uric acid,body mass index,glucose,creatinine,triglycerides,diastolic blood pressure,high density lipoprotein and low density lipoprotein in the hyperuricemia group were higher than those in the control group,and the differences were statistically significant(P<0.05).The gene rs2231142(G/T)loci met the HWE equilibrium test of the two groups(P>0.05),indicating that the locus is representative of the population.There were statistically significant differences in the distribution frequencies of GG,GT,and TT genotypes in the hyperuricemia group and healthy control group(χ2=17.146,P<0.001),and there were also statistically significant differences in the distribution frequencies of alleles G and T between the two groups(χ2=19.115,P<0.001).TT genotypes were expressed as risk factors for hyperuricemia in different genetic models(additive model OR=2.302,95%CI:1.472-3.603;explicit model OR=1.689,95%CI:1.283-2.210;recessive model OR=1.867,95%CI:1.221-2.874).The differences in uric acid,glucose and triglycerides among the different genotype subgroups were statistically significant(P<0.05).

关 键 词：高尿酸血症 ABCG2基因 单核苷酸多态性 荧光素酶分析 

分 类 号：R181[医药卫生—流行病学]