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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2018, Vol. 07 ›› Issue (05) : 203 -206. doi: 10.3877/cma.j.issn.2095-3216.2018.05.003

所属专题： 文献；

论著

Klotho G-395A基因多态性与ESRD患者钙磷代谢紊乱的相关性分析
曾庆亚1, 佟颜杉2, 孙亮2, 牟洪宾2, 陈蕊2, 毕光宇2, 刘昌华2,†()   
  1. 1. 116023　辽宁省，大连医科大学第二临床学院；225009　江苏省，扬州大学临床医学院　江苏省苏北人民医院肾内科
    2. 225009　江苏省，扬州大学临床医学院　江苏省苏北人民医院肾内科
  • 收稿日期:2018-01-05 出版日期:2018-10-28
  • 通信作者: 刘昌华
  • 基金资助:
    扬州市科技局社发项目(SQZ201430047)

Correlation analysis between klotho G-395A polymorphism and calcium and phosphorus metabolic disorders in ESRD patients

Qingya Zeng1, Yanshan Tong2, Liang Sun2, Hongbin Mou2, Rui Chen2, Guangyu Bi2, Changhua Liu2,†()   

  1. 1. 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
    2. Department of Nephrology, Jiangsu Provincial Subei People′s Hospital, Yangzhou University Clinical College, Yangzhou 225009, Jiangsu Province; China
  • Received:2018-01-05 Published:2018-10-28
  • Corresponding author: Changhua Liu
  • About author:
    Corresponding author: Liu Changhua, Email:
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引用本文：

曾庆亚, 佟颜杉, 孙亮, 牟洪宾, 陈蕊, 毕光宇, 刘昌华. Klotho G-395A基因多态性与ESRD患者钙磷代谢紊乱的相关性分析[J]. 中华肾病研究电子杂志, 2018, 07(05): 203-206.

Qingya Zeng, Yanshan Tong, Liang Sun, Hongbin Mou, Rui Chen, Guangyu Bi, Changhua Liu. Correlation analysis between klotho G-395A polymorphism and calcium and phosphorus metabolic disorders in ESRD patients[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2018, 07(05): 203-206.

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(TaqMan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、Mann-Whitney 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

①ESRD组和健康对照组的基因型分布均符合Hardy-Weinberg平衡(χ2＝0.512, χ2＝0.134; P<0.05)。②ESRD组和对照组基因亚型及基因频率分布差异有统计学意义(χ2 ＝11.467, P＝0.003; χ2＝10.130, P＝0.001)，且ESRD组患者A等位基因频率较对照组高。③ESRD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。

关键词: 终末期肾病, klotho基因多态性, 钙磷代谢, Klotho蛋白
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.

Results

① The genotypes distributions of the ESRD group and the healthy control group were consistent with the Hardy-Weinberg equilibrium (χ2=0.512, χ2 =0.134; P<0.05). ② There were significant differences in gene subtypes and gene frequency distributions between the ESRD group and the control group (χ2=11.467, P=0.003; χ2=10.130, P=0.001), and the A allele frequency was higher in the ESRD group than in the control group. ③ There 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). ④ Binary 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.

Key words: End-stage renal disease, Klotho polymorphism, Calcium and phosphorus metabolism, Klotho protein
表1 ESRD组和对照组klotho基因型及基因频率的比较
组别 总例数 G-395A基因型(例) G-395A等位基因频率(%)
GG GA AA G A
对照组 80 48 27 05 123(76.8) 37(23.2)
ESRD组 137 50 70 17 170(62.0) 104(38.0)
χ2值 ? 11.467 10.130
P值 ? 0.003 0.001
表2 ESRD组与对照组一般资料及各临床生化指标比较
组别 例数 年龄(岁) 性别(男/女) BMI(kg/m2) 血红蛋白(g/L) 白蛋白(g/L)
对照组 80 55.42±13.66 42/38 22.1(20.7～23.5) 131.31±6.09 45.60±5.71
ESRD组 137 56.36±13.58 88/49 22.2(20.4～23.7) 86.71±21.40 38.17±5.84
t/Z值 ? －0.49 2.90 －0.233 18.19 9.10
P值 ? 0.624 0.089 0.816 <0.001 0.000
? 钙(mmol/L) 磷(mmol/L) iPTH(ng/L) FGF23(μg/L ) Klotho(μg/L)
对照组 2.24±0.14 1.32(1.13，1.43) 35.0(27.3～44.0) 66.5(54. 7～78.5) 48.89(43.1～56.9)
ESRD组 1.99±0.20 1.78(1.62～1.89) 254.0(176.0～367.2) 303.2(209.3～382.7) 19.5(14.5～26.7)
t/Z值 9.49 －10.507 －12.28 －12.01 －11.618
P值 <0.001 <0.001 <0.001 <0.001 <0.001
表3 ESRD患者中G-395A不同基因型间的一般资料及临床生化指标比较
基因型 例数 年龄(岁) 性别(男/女) BMI(kg/m2) 血红蛋白(g/L) 白蛋白(g/L)
GG 50 54.82±16.10 29/21 22.5(20.7～24.3) 82.02±19.90 37.11±5.92
GA 70 58.67±10.85 46/24 22.1(20.3～23.9) 90.74±19.09 38.70±5.87
AA 17 51.41±14.43 13/4 21.2(19.2～23.1) 83.94±31.02 39.10±5.41
F/χ2值 ? 2.514 2.021 3.761 2.942 1.339
P值 ? 0.093 0.364 0.152 0.064 0.266
基因型 例数 钙(mmol/L) 磷(mmol/L) iPTH(ng/L) FGF23(μg/L) Klotho(μg/L)
GG 50 1.99±0.21 1.81(1.62～1.89) 246.0(165.4～187.9) 287.7(199.4～387.5)c 22.0(17.5～26.4)c
GA 70 2.03±0.19c 1.73(1.61～1.88) 254.0(187.9～390.1) 293.1(205.9～358.6)c 19.5(15.3～27.0)c
AA 17 1.90±0.18b 1.88(1.69～2.02) 348.2(148.0～904.5) 404.5(322.6～501.0)ab 10.1(8.2～12.4)ab
F/χ2值 ? 3.075 5.027 3.407 19.780 35.117
P值 ? 0.049 0.081 0.182 <0.001 <0.001
表4 ESRD并发钙磷代谢紊乱相关因素的Logistic回归分析
自变量 B S.E. Wald P Exp(B) EXP(B)的95%CI
下限 上限
GA＋AA 1.447 0.619 5.458 0.019 4.249 1.262 14.304
FGF23 0.013 0.004 9.551 0.002 1.013 1.005 1.022
Klotho 0.020 0.034 0.372 0.542 1.021 0.956 1.090
年龄(岁) 0.006 0.022 0.080 0.777 1.006 0.964 1.050
iPTH(ng/L) 0.001 0.002 0.340 0.560 1.001 0.997 1.005
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