摘要
目的观察终末期肾病(ESRD)患者klotho G-395A基因多态性分布与其合并钙磷代谢紊乱的相关性。方法选取2015年4月至2016年12月期间就诊于扬州市多个血液净化中心的ESRD患者共137例,体检中心正常体检者80名为对照组;运用FQ-PCR(Taq Man法)对各研究对象进行klotho基因G-395A多态性分型;检测klotho蛋白、成纤维细胞生长因子(FGF23)及钙磷代谢相关生化指标水平,比较不同基因型间各生化指标间的水平。卡方检验、t检验、单因素方差分析、MannWhitney U检验及Kruskal-Wallis H检验用于各组生化指标间差异性分析,多因素采用二元logistic回归分析。结果 (1)ESRD组和健康对照组的基因型分布均符合Hardy-Weinberg平衡(χ~2=0. 512,χ~2=0. 134; P <0. 05)。(2)ESRD组和对照组基因亚型及基因频率分布差异有统计学意义(χ~2=11. 467,P=0. 003;χ~2=10. 130,P=0. 001),且ESRD组患者A等位基因频率较对照组高。(3)ESRD组不同的基因型中,血钙、klotho蛋白及FGF23水平差异有统计学意义(P <0. 05),血钙在GA型与AA型间表达水平差异有统计学意义(t=-2. 469,P=0. 015),FGF23、klotho蛋白在GG与AA型(Z=-4. 020,Z=-5. 461; P <0. 001),GA与AA型(Z=-4. 303,Z=-5. 610; P <0. 001)之间的表达水平差异均有统计学意义。(4)二元logistic回归分析示GA+AA型为ESRD患者钙磷代谢紊乱的独立危险因素。结论 Klotho G-395A基因多态性A等位基因位点可能为ESRD患者的易感基因,并与ESRD患者合并钙磷代谢紊乱有关。
Objective To explore the correlation between klotho G^-395A polymorphism and calcium and phosphorus metabolic disorders in end-stage renal disease(ESRD)patients.Methods A total of 137 patients with ESRD who were admitted to the Yangzhou Multi-central Blood Purification Center from April 2015 to December 2016 were selected.80 people with normal physical examination from the physical examination center were enrolled as control.The klotho G^-395A polymorphism was analyzed with TaqMan FQ-PCR method.The levels of klotho protein,fibroblast growth factor(FGF23),and calcium and phosphorus metabolism-related biochemical indicators were also measured and compared.Chi-square test,t-test,one-way ANOVA,Mann-Whitney U test,and Kruskal-Wallis H test were used to analyze the differences.The binary logistic regression method was performed for multivariate analysis.Results①The genotypes distributions of the ESRD group and the healthy control group were consistent with the Hardy-Weinberg equilibrium(χ^2=0.512,χ^2=0.134;P<0.05).②There were significant differences in gene subtypes and gene frequency distributions between the ESRD group and the control group(χ^2=11.467,P=0.003;χ^2=10.130,P=0.001),and the A allele frequency was higher in the ESRD group than in the control group.③There were significant differences in serum calcium,klotho protein,and FGF23 levels among different genotypes of the ESRD group(P<0.05).There was a statistically significant difference in the level of serum calcium between the GA and the AA types(t=-2.469,P=0.015).There were statistically significant differences in the expression levels of FGF23 and klotho proteins between the GG and the AA types(Z=-4.020,Z=-5.461;P<0.001),as well as between the GA and the AA types(Z=-4.303,Z=-5.610;P<0.001).④Binary logistic regression analysis showed that GA+AA type was an independent risk factor for calcium and phosphorus metabolism disorders in the ESRD patients.Conclusion The klotho G-395A polymorphism A allele locus might be a susceptibility gene for the ESRD patients,and was related to the calcium and phosphorus metabolism disorders in the ESRD patients.
作者
曾庆亚
佟颜杉
孙亮
牟洪宾
陈蕊
毕光宇
刘昌华
Zeng Qingya;Tong Yanshan;Sun Liang;Mou Hongbin;Chen Rui;Bi Guangyu;Liu Changhua(Dalian Medical University Second Clinical College,Dalian 116023,Liaoning Province;Department of Nephrology,Jiangsu Provincial Subei People′s Hospital,Yangzhou University Clinical College,Yangzhou 225009,Jiangsu Province,China)
出处
《中华肾病研究电子杂志》
2018年第5期203-206,共4页
Chinese Journal of Kidney Disease Investigation(Electronic Edition)
基金
扬州市科技局社发项目(SQZ201430047)