Klotho基因G-395A多态性与慢性肾脏病的相关性分析

The relationship between Klotho G-395A gene polymorphism and pathogenesis of chronic kidney disease

目的探讨Klotho基因G-395A多态性与慢性肾脏病(chronic kidney disease,CKD)的关系。方法选取2017年1-10月在中南大学湘雅医学院附属海口医院肾病风湿科治疗的CKD患者214例,按血肌酐水平将所有患者分为血肌酐水平正常组(147例)和血肌酐水平异常组(67例),同时选取健康志愿者100例作为对照组。检测各组Klotho基因G-395A位点基因型和等位基因,并进行比较分析。结果对照组基因型GA+AA型比例、等位基因A比例分别为14.00%和8.00%,明显高于血肌酐水平正常组、血肌酐水平异常组,差异有统计学意义(P<0.05)。血肌酐水平正常组、血肌酐水平异常组基因型GA+AA型比例与等位基因A比例比较,差异无统计学意义(P>0.05)。血肌酐水平正常组中,体质量指数(body mass index,BMI)<25患者与BMI≥25患者的Klotho基因G-395A基因型和等位基因分布比较,差异无统计学意义(P>0.05);血肌酐水平异常组中,GA基因型患者胰岛素抵抗指数和尿白蛋白排泄率分别为(2.11±0.40)、(167.28±20.54)mg/24 h,明显低于GG基因型患者,差异有统计学意义(P<0.05)。非条件logistic回归分析显示G-395A位点GG+GA基因型的OR=2.004,95%CI=1.227~3.274,提示G-395A位点的GG+GA基因型是CKD的危险因素。结论 Klotho基因G-395A位点多态性A等位基因可能是人的保护基因,而G基因型可能是CKD的致病基因。

Objective To investigate the relationship between Klotho G-395A gene polymorpohism and chronic kidney disease （CKD）. Methods Two hundred and fourteen patients with CKD who received medical care in the Department of RheumatisM1, Haikou Hospital from January to October, 2017 were recruited as the research subjects, and were divided into the normal serum creatinine group （or the CKD-1 group） （147 patients） and the abnormal serum creatinine group （or the CKD-2 group） （67 patients ）, in accordance with the levels of serum creatinine. Another 100 healthy volunteers were assigned as the control group. Klotho gene G-395A genotype and allele of the 3 groups were detected, and comparisons and analyses were made between the 3 groups. Results The percentages of genotype GA ＋ AA and allele A in the control group were respectively 14% and 8%, which were significantly higher than those in the CKD-1 and the CKD-2 groups, with statistical significance （P 〈 0.05 ）. There were no significant differences in the percentages of gen- otype GA ＋ AA and the percentages of allele A, when comparisons were made between the CKD-1 and CKD-2 groups （P 〈 0.05）. For the CKD-1 group, there was no statistical significance, when comparisons were made in the distribution of Klotho gene G-395A genotype and allele between the patients with body- mass index（BMI）. BMI 〈25 and BMI≥25（P 〉0.05）. For the CKD-2 group, the insulin re- sistance index and urinary albumin excretion rate of GA genotype were respectively （2.11 ±0.40） and （ 167.28 ±20.54） rag/24 h, which were significantly lower than those of the GG genotype patients, with statistical significance （P 〈 0.05 ）. Non-conditional Logisticregression analysis showed that the OR of G395A site GG ＋ GA genotype was 2. 004, and 95% confidence interval （CI） was 1. 227- 3. 274, indicating that GG ＋ GA genotype was a risk factor for CKD. Conclusion Klotho gene G-395A polymorphism allele A might be a protective factor for humans, while genotype G might be a pathogenic gene of CKD.