本文選題：klotho基因　切入點：單核苷酸多態(tài)性　出處：《揚州大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:研究CKD5期患者Klotho基因多態(tài)性及其表達蛋白與鈣磷代謝紊亂的相關性。方法:研究組(B組)為200名CKD5期患者,根據不同腎臟替代治療方式將B組患者分為未透析組(B0組)、血液透析組(B1組)、腹膜透析組(B2)三組;對照組(A組)為80名同期健康體檢者,采集A、B組病人的靜脈血。分析A組和B組Klotho基因G-395A位點的基因型分布、等位基因頻率的差異性,同時對CKD5期各亞組Klotho蛋白水平進行比較,并分析klotho蛋白其與鈣磷代謝相關指標的相關性。結果:(1)研究對象klotho基因G-395A位點的基因型分布均符合Hardy-Weinberg平衡,具有群體代表性。(2)A組與B組患者G-395A基因型分布與等位基因頻率比較有差異性(P0.05),CKD5期組(B組)GA+AA基因型頻率及A等位基因頻率均高于對照組(A組)(P0.05)。(3)CKD5期組(B組)血漿klotho蛋白水平顯著低于健康對照組(A組),差異具有統(tǒng)計學意義(P0.01)。亞組分析顯示,B0、B1與B2三組之間血鈣水平差異有統(tǒng)計學差異(P0.05),血磷、Klotho蛋白及FGF23水平,三組之間差異無統(tǒng)計學差異(P0.05)。(4)在未透析患者(B0組)中,與GG基因型比較,GA+AA基因型血鈣水平偏低,差異有統(tǒng)計學意義(P=0.034),而血磷水平則偏高,差異有統(tǒng)計學意義(P=0.027);在血透患者(B1組)及腹透患者(B2組)中,與GG基因型比較,GA+AA基因型血鈣水平偏低,差異有統(tǒng)計學差異(P=0.009,P=0.002);而CKD5期各亞組之間比較,血漿klotho蛋白及FGF23水平的差異均無統(tǒng)計學意義(P0.05)。(5)CKD5期各亞組患者血漿klotho蛋白水平均與FGF23水平呈負相關,差異均有統(tǒng)計學意義(P0.01;P0.01;P=0.001)。未透析組(B0組)及血透組(B1組)患者血漿klotho蛋白水平與血鈣水平均呈正相關(r=0.449,P0.01;r=0.394,P=0.02),與血磷水平均呈負相關(r=-0.624,P0.01;r=-0.406,P=0.001);與血清甲狀旁腺激素水平無相關性(r=-0.118,P=0.239;r=-0.037,P=0.784);腹透組(B2組)患者血漿klotho蛋白水平與血鈣和血磷水平均無相關性(r=0.310,P=0.055;r=-0.282,P=0.082),與血清甲狀旁腺激素水平呈負相關(r=-0.335,P=0.037)。(6)Logistic 回歸分析顯示,GA+AA 基因型(OR=5.962,95%CI 3.281-10.832,P0.01)、血漿 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)與CKD患者并發(fā)鈣磷代謝紊亂具有相關性。結論:(1)在研究人群中存在Klotho基因G-395A多態(tài)性,其中GA+AA基因型在CKD5期并發(fā)鈣磷代謝紊亂患者中多見。(2)klotho基因G-395A位點GA+AA基因型可能與CKD5期患者并發(fā)鈣磷代謝紊亂有關。(3)klotho蛋白和FGF23參與了 CKD患者的鈣磷代謝調節(jié),且klotho蛋白可能是CKD5期患者并發(fā)鈣磷代謝紊亂的保護因素;FGF23水平升高可能是CKD5期患者并發(fā)鈣磷代謝紊亂的獨立危險因素。
[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.
【學位授予單位】：揚州大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R692

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