VDR基因FokI多态性与云南汉族2型糖尿病肾病的易感性研究及血浆CysC、Hcy、sICAM-1对早期DN检测的临床价

发布时间：2018-02-20 22:00

本文关键词： 单核苷酸多态性糖尿病糖尿病肾病受体骨化三醇糖尿病肾病同型半胱氨酸半胱氨酸蛋白酶抑制剂细胞间粘附分子-1 尿微量白蛋白早期诊断　出处：《昆明医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：第一部分维生素D受体基因FokI(T/C)多态性与云南汉族2型糖尿病肾病的易感性研究[目的]探讨维生素D受体FokI基因单核苷酸多态性在云南汉族2型糖尿病患者的分布情况,并探讨其与2型糖尿病及糖尿病肾病易感性之间的关系。[方法]采用病例对照的研究方法对云南汉族91例糖尿病病程大于10年的2型糖尿病不伴肾病患者(DM组)、89例糖尿病病程小于10年2型糖尿病合并糖尿病肾病患者(DN组)及96例健康对照者(NC组)进行研究,比较三组间25羟维生素D浓度,用QPCR-taqman探针法对维生素D受体基因FokI位点基因型及等位基因频率进行检测,并分析与糖尿病肾病的易感性。[结果](1)NC组25(OH)D血浆浓度显著高于DN组、DM组(p值分别为0.00,0.00)；(2)25(OH)D浓度与年龄、BMI、糖化血红蛋白、TG呈负相关关系(r值分别为-0.25,-0.24,-0.35,-0.29,P均0.001)；(3)FokI基因型分布在DM与DN组、DM组和DN组间差异无统计学意义(P0.05)；和NC组比,DN组FF基因型频率相对低,且差异有统计学意义(χ2=3.45, P=0.045), ff, Ff基因型未见差异(P0.05)；和DM组比,f等位基因频率在DN组高,占53.4%,(RR=1.46,P0.05)；(4)Logistic回归分析结果提示ff基因型是DN的易感因素(P=0.04,OR=2.37)。[结论]我国云南汉族人群以Ff基因型为主,Fokl位点ff基因型可能是云南地区汉族2型糖尿病肾病的易感基因。第二部分血浆Cys-C、Hey、sICAM-1对糖尿病肾病早期检测的临床价值[目的]研究同型半胱氨酸(Hcy)、胱抑素(Cys C)、可溶性细胞间粘附分子-1 (sICAM-1)在2型糖尿病及糖尿病肾病患者血浆中水平的变化,探讨各生化指标检测阳性率对糖尿病肾病早期的意义。[方法]以尿微量白蛋白肌酐比值(ACR)为糖尿病肾病诊断的金标准将180例2型糖尿病受试者分为NDN组和DN组,以90例正常人作为对照组(NC组),比较三组间Hey、CysC、sICAM-1水平的差异,与UACR的关系,并做ROC曲线,计算其阳性率及特异性。[结果](1)DN组Hey、CysC、sICAM-1和UACR水平均高于NC组,差异有统计学意义(P均0.01),且高于NDN组,p值均0.05；NDN组Hey、CysC水平高于NC组(P0.05),sICAM-1在两组间未见统计学差异(P0.05)；(2)DN组Hey、CysC、sICAM-1阳性率分别为81.11%、56.7%、10%,特异度分别为47.7%、77.8%、97.7%,联合检测阳性率为88.8%,各指标ROC曲线下面积分别为0.74、0.78、0.72,P值均小于0.05；(3) Hcy、CysC、sICAM-1水平与UAER呈正相关(r值分别为0.45、0.65、0.32,p均0.05)。[结论](1)糖尿病肾病早期Hey、CysC水平已异常升高,sICAM-1可能参与了糖尿病肾病的进展,且Hey、CysC、sICAM-1与ACR呈正相关关系,(2)较单项检测而言,Hey、CysC、sICAM-1三者联合检测可提高糖尿病肾病早期检出率。
[Abstract]:Part one: study on the relationship between vitamin D receptor gene FokIr T / C polymorphism and susceptibility to type 2 diabetic nephropathy in Yunnan Han nationality [objective] to investigate the distribution of single nucleotide polymorphism of vitamin D receptor FokI gene in type 2 diabetes mellitus patients of Yunnan Han nationality. To explore the relationship between type 2 diabetes mellitus and susceptibility to diabetic nephropathy. [methods] 91 patients with type 2 diabetes without nephropathy who had a course of more than 10 years of diabetes mellitus in Yunnan Han nationality were studied by a case-control study. The course of diabetes was less than 10 years in type 2 diabetic patients with diabetic nephropathy (DN group) and 96 healthy controls (NC group). The genotypes and allelic frequencies of FokI locus of vitamin D receptor gene were detected by QPCR-taqman probe method compared with the concentration of 25 hydroxyvitamin D between the three groups. And to analyze the susceptibility to diabetic nephropathy. [results] the plasma concentration of 25 OHHG in NC group was significantly higher than that in DM group of DN group (P = 0.000. 000) and BMI.There was a negative correlation between TG and glycosylated hemoglobin triglyceride (TG). The results showed that there was a negative correlation between plasma concentration and BMIs in diabetic nephropathy group (P = -0.25-0.24- 0.35- 0.29) and the distribution of FokI genotype in DM group was 0.001FokI genotype. There was no significant difference between DM group and DN group (P 0.05), and the frequency of FF genotype in NC group was lower than that in DN group. The difference was statistically significant (蠂 2 3.45, P 0. 045, F, F, P 0. 05, P 0. 05), and the frequency of allele in DM group was higher than that in DN group. Logistic regression analysis showed that the ff genotype was the predisposing factor of DN. [conclusion] the F f genotype is the main Fokl locus ff genotype in Yunnan Han population, which may be the susceptible gene of type 2 diabetic nephropathy in the Han nationality of Yunnan. The clinical value of the second part of plasma Cys-Ctin-Heysis-ICAM-1 in the early detection of diabetic nephropathy [objective] to study the changes of plasma levels of homocysteine, cystatin, cystatin, and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with type 2 diabetes mellitus and diabetic nephropathy. To explore the significance of positive rate of each biochemical index in the early stage of diabetic nephropathy. [methods] 180 patients with type 2 diabetes mellitus were divided into NDN group and DN group by using urinary albumin creatinine ratio (NDN) as the gold standard for the diagnosis of diabetic nephropathy. 90 normal controls were used as control group to compare the difference of CysCnsICAM-1 level between the three groups, the relationship between CysCnsICAM-1 and UACR, and the ROC curve to calculate the positive rate and specificity. [results] the levels of CysCnsICAM-1 and UACR in the patients with DN were higher than those in the NC group. The difference was statistically significant (P = 0.01), and higher than that in NDN group (P = 0.05). The level of CysC was higher than that in NC group (P 0.05). There was no statistical difference between the two groups. The positive rate of CysCsICAM-1 in the DN group was 81.111.115.76.71010, and the specificity was 47.77.87.77.77.77.77.70.The positive rate of ROC was 88.8. The area under the curve was 0.74 卤0.78 / 0.72 P < 0.05 ~ 3) the level of cystoma CysCnsICAM-1 was positively correlated with UAER, respectively. [conclusion] in the early stage of diabetic nephropathy, the level of Hey CysC has been increased abnormally and the level of sICAM-1 may be involved in the progression of diabetic nephropathy, and the positive correlation between ICAM-1 and UAER is 0. 45 卤0. 65. [conclusion] the level of Hey CysC in early diabetic nephropathy may be involved in the progression of diabetic nephropathy. There was a positive correlation between CysCnsICAM-1 and ACR. (2) the combined detection of CysCnsICAM-1 could improve the detection rate of early diabetic nephropathy.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.2

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