CKD5期患者klotho基因多态性及其表达蛋白与钙磷代谢紊乱的相关性

发布时间：2018-03-08 05:20

本文选题：klotho基因　切入点：单核苷酸多态性　出处：《扬州大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:研究CKD5期患者Klotho基因多态性及其表达蛋白与钙磷代谢紊乱的相关性。方法:研究组(B组)为200名CKD5期患者,根据不同肾脏替代治疗方式将B组患者分为未透析组(B0组)、血液透析组(B1组)、腹膜透析组(B2)三组;对照组(A组)为80名同期健康体检者,采集A、B组病人的静脉血。分析A组和B组Klotho基因G-395A位点的基因型分布、等位基因频率的差异性,同时对CKD5期各亚组Klotho蛋白水平进行比较,并分析klotho蛋白其与钙磷代谢相关指标的相关性。结果:(1)研究对象klotho基因G-395A位点的基因型分布均符合Hardy-Weinberg平衡,具有群体代表性。(2)A组与B组患者G-395A基因型分布与等位基因频率比较有差异性(P0.05),CKD5期组(B组)GA+AA基因型频率及A等位基因频率均高于对照组(A组)(P0.05)。(3)CKD5期组(B组)血浆klotho蛋白水平显著低于健康对照组(A组),差异具有统计学意义(P0.01)。亚组分析显示,B0、B1与B2三组之间血钙水平差异有统计学差异(P0.05),血磷、Klotho蛋白及FGF23水平,三组之间差异无统计学差异(P0.05)。(4)在未透析患者(B0组)中,与GG基因型比较,GA+AA基因型血钙水平偏低,差异有统计学意义(P=0.034),而血磷水平则偏高,差异有统计学意义(P=0.027);在血透患者(B1组)及腹透患者(B2组)中,与GG基因型比较,GA+AA基因型血钙水平偏低,差异有统计学差异(P=0.009,P=0.002);而CKD5期各亚组之间比较,血浆klotho蛋白及FGF23水平的差异均无统计学意义(P0.05)。(5)CKD5期各亚组患者血浆klotho蛋白水平均与FGF23水平呈负相关,差异均有统计学意义(P0.01;P0.01;P=0.001)。未透析组(B0组)及血透组(B1组)患者血浆klotho蛋白水平与血钙水平均呈正相关(r=0.449,P0.01;r=0.394,P=0.02),与血磷水平均呈负相关(r=-0.624,P0.01;r=-0.406,P=0.001);与血清甲状旁腺激素水平无相关性(r=-0.118,P=0.239;r=-0.037,P=0.784);腹透组(B2组)患者血浆klotho蛋白水平与血钙和血磷水平均无相关性(r=0.310,P=0.055;r=-0.282,P=0.082),与血清甲状旁腺激素水平呈负相关(r=-0.335,P=0.037)。(6)Logistic 回归分析显示,GA+AA 基因型(OR=5.962,95%CI 3.281-10.832,P0.01)、血浆 klotho 蛋白水平(OR=0.892,95%CI0.813-0.978,P=0.015)和 FGF23 水平(OR=1.115,95%CI 1.055-1.179,P0.01)与CKD患者并发钙磷代谢紊乱具有相关性。结论:(1)在研究人群中存在Klotho基因G-395A多态性,其中GA+AA基因型在CKD5期并发钙磷代谢紊乱患者中多见。(2)klotho基因G-395A位点GA+AA基因型可能与CKD5期患者并发钙磷代谢紊乱有关。(3)klotho蛋白和FGF23参与了 CKD患者的钙磷代谢调节,且klotho蛋白可能是CKD5期患者并发钙磷代谢紊乱的保护因素;FGF23水平升高可能是CKD5期患者并发钙磷代谢紊乱的独立危险因素。
[Abstract]:Objective: to study the association of Klotho gene polymorphism and its expression protein with calcium and phosphorus metabolic disorder in patients with CKD5. According to different methods of renal replacement therapy, group B was divided into three groups: group B _ 0 without dialysis, group B _ 1 with hemodialysis and group B _ 2 with peritoneal dialysis. The venous blood samples were collected from patients in group A and group B. the genotype distribution and allele frequency of G-395A locus of Klotho gene in group A and group B were analyzed, and the Klotho protein levels of each subgroup in CKD5 phase were compared. The relationship between klotho protein and calcium and phosphorus metabolism was analyzed. Results: the genotype distribution of G-395A locus of klotho gene in all subjects was in accordance with Hardy-Weinberg equilibrium. The difference of G-395A genotype distribution and allele frequency between group A and group B is significant. The frequency of GA AA genotype and A allele in group B is higher than that in group A (P 0.05) and group B (group B)) plasma klotho is higher than that in control group (P < 0.05). The frequency of allele A in group B is higher than that in group A (P 0.05N) and the frequency of allele A in group B is higher than that in group B (P < 0.05). The protein level was significantly lower than that in the healthy control group A (P 0.01). The subgroup analysis showed that there were significant differences in serum calcium levels between B0B _ 1 and B _ 2 groups (P 0.05), and the levels of Klotho protein and FGF23 in the blood of B0B _ (B1) and B _ (2) were significantly lower than those in the healthy control group (P < 0.05). There was no significant difference among the three groups (P 0.05) in group B _ 0 (P < 0.05), compared with GG genotype, the serum calcium level of GA AA genotype was lower than that of GG genotype, the difference was statistically significant (P < 0.05), but the blood phosphorus level was higher than that of GG genotype. The difference was statistically significant (P < 0.027); in hemodialysis group B _ 1 and abdominal dialysis group B _ 2), the blood calcium level of GA AA genotype was lower than that of GG genotype, and the difference was statistically significant (P 0.009 P ~ (0.002)), while in the CKD5 phase, the blood calcium levels were lower than those of GG genotype, and there was a significant difference among the subgroups in the CKD5 phase. There was no significant difference in plasma klotho protein and FGF23 levels. The plasma klotho protein levels were negatively correlated with FGF23 levels in all subgroups. There was a significant difference between plasma klotho protein level and serum calcium level in patients without dialysis or in hemodialysis group B _ 1). There was a positive correlation between plasma klotho protein level and serum calcium level. There was a negative correlation between plasma klotho protein protein level and serum phosphorus level. There was no correlation between plasma klotho protein protein level and serum parathyroid hormone level, but there was no correlation between serum parathyroid hormone level and serum phosphorus level. There was no correlation between plasma klotho protein level, serum calcium and phosphorus levels, and a negative correlation between serum parathyroid hormone level and serum parathyroid hormone level. Logistic regression analysis showed that GA-AA AA genotype OR5.962CI 3.281-10.832 P0.01, and plasma klotho protein level 0.89295CI0.88-0.97P0. 015) and 0.89295CI 3.281-10.832P0.01, 0.89295.95 CI 3.281-10.832P0.01and 0.89295CI0.888P0. 015) and the results of logistic regression analysis showed that there was no correlation between plasma klotho protein level and serum parathyroid hormone level (P < 0.05). The results of logistic regression analysis showed that GA-AA AA genotype OR5.962CI 3.281-10.832P0.01and plasma klotho protein level were 0.89295CI0.813-0.97P0. 015). There is a correlation between FGF23 level and calcium and phosphorus metabolism disorder in CKD patients. Conclusion the G-395A polymorphism of Klotho gene exists in the study population. The GA-AA genotype at G-395A locus of the G-395A locus of the GA-AA genotype in the patients with calcium and phosphorus metabolism disorder in CKD5 stage may be related to the calcium and phosphorus metabolic disorder in patients with CKD5. The protein and FGF23 may be involved in the regulation of calcium and phosphorus metabolism in the patients with CKD, and the GA-AA genotype may be involved in the regulation of calcium and phosphorus metabolism in the patients with CKD. Klotho protein may be the protective factor of calcium and phosphorus metabolism disorder in patients with CKD5. The increase of FGF23 level may be an independent risk factor of calcium and phosphorus metabolism disorder in CKD5 patients.
【学位授予单位】：扬州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692

【相似文献】