新疆维吾尔族T2DM患者FOSL2基因表达及其DNA甲基化分析

发布时间：2018-07-02 22:15

本文选题：2型糖尿病 + 新疆维吾尔族　；参考：《石河子大学》2015年硕士论文

【摘要】：目的:采用逆转录聚合酶链式反应(RT-PCR)及基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术等探讨FOSL2基因表达及其DNA甲基化情况在新疆维吾尔族2型糖尿病(T2DM)发病机制中的作用。方法:1.收集2013年09月-2014年03月间新疆维吾尔自治区喀什地区莎车县维吾尔族T2DM与维吾尔族非DM患者病例各50例,测定记录其一般资料,包括性别、年龄、身高、体重、腰围、臀围、血压、糖尿病病程等一般临床基线资料,根据公式计算出腰臀比(WHR)、体重指数(BMI)。采集研究对象空腹静脉血标本经肝素抗凝,使用全自动生化分析仪测定空腹血糖(FPG)、血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL)等生化指标,高压液相法测定糖化血红蛋白(Hb A1c);2.采用RT-PCR法检测FOSL2基因m RNA表达水平;3.采用MALDI-TOF MS法检测外周血白细胞FOSL2基因DNA甲基化水平;4.采用SPSS17.0统计软件进行数据处理。计量资料用均数±标准差表示,两组间均数比较采用t检验。两组间甲基化率比较运用两个独立样本的Wilcoxon秩和检,变量之间的相关关系采用多元线性回归分析,,以P0.05为差异有统计学意义。结果:1.与新疆维吾尔族非DM组相比,新疆维吾尔族T2DM组在年龄、性别比、收缩压(SBP)、舒张压(DBP)、WHR等一般基线资料无统计学差异(P0.05),说明基线齐,资料具有可比性;2.与新疆维吾尔族非DM组相比,新疆维吾尔族T2DM组患者FOSL2基因m RNA表达水平明显降低(2.456±0.512,0.996±0.159;P0.01);3.与新疆维吾尔族非DM病组相比,新疆维吾尔族T2DM组患者FOSL2基因CPG Unit3(CPG_3)(0.016±0.004,0.030±0.003;P0.01)、CPG Unit4(CPG_4.5)(0.065±0.006,0.095±0.007;P0.05)、CPG Unit5(CPG_6.7)(0.002±0.001,0.014±0.002;P0.01)、CPG Unit6(CPG_8)(0.004±0.001,0.023±0.003;P0.01)、CPG Unit8(CPG_11)(0.002±0.001,0.029±0.003;P0.01)、CPG Unit9(CPG_12.13.14)(0.092±0.004,0.119±0.003;P0.01)、CPG Unit10(CPG_15.16.17)(0.008±0.002,0.019±0.001;P0.01)DNA的甲基化率均较高;4.在新疆维吾尔族T2DM组中,以FOSL2基因DNA平均甲基化率为应变量,患者的年龄、身高、体重、腰围、臀围、WHR、BMI、脉率、SBP、DBP、FPG、Hb A1c、TC、TG、LDL、HDL等指标为自变量进行多元线性回归分析,结果显示患者身高、体重、BMI、脉率、SBP、FPG、Hb A1c进入回归方程。回归方程:y=-1.521+0.007(身高)-0.006(体重)+0.018(BMI)+0.001(脉率)+0.001(SBP)-0.003(FPG)+0.004(Hb A1c)。结论:1.FOSL2基因可能与新疆维吾尔族T2DM、肥胖及糖脂代谢的异常相关。2.FOSL2基因DNA多个位点的高甲基化可能致使其m RNA表达水平的下调,参与新疆维吾尔族T2DM的发生与发展。
[Abstract]:Objective: to investigate the role of FOSL2 gene expression and DNA methylation in the pathogenesis of type 2 diabetes mellitus (T2DM) in Xinjiang Uygur nationality by reverse transcription polymerase chain reaction (RT-PCR) and matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Method 1: 1. From September 2013 to March 2014, 50 Uygur patients with T2DM and 50 Uygur non-DM patients were collected from Shacha County, Kashi County, Xinjiang Uygur Autonomous region, and their general data including gender, age, height, weight, waist circumference and hip circumference were measured and recorded, including sex, age, height, weight, waist circumference and hip circumference. The general clinical baseline data such as blood pressure, diabetes course and so on. WHR and BMI were calculated according to the formula. Fasting venous blood samples were collected by heparin anticoagulant. Fasting blood glucose (FPG), serum cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL) were measured by automatic biochemical analyzer. Determination of glycosylated hemoglobin (HB A 1c) by high pressure liquid chromatography. The mRNA expression level of FOSL2 gene was detected by RT-PCR. The DNA methylation level of FOSL2 gene in peripheral blood leukocytes was detected by MALDI-TOF MS. SPSS 17.0 statistical software was used to process the data. The measurement data were expressed as mean 卤standard deviation. T test was used to compare the mean between the two groups. The methylation rate of the two groups was compared by Wilcoxon rank sum test of two independent samples and the correlation between the variables was analyzed by multiple linear regression analysis. The difference was statistically significant with P0.05. The result is 1: 1. There was no statistical difference in age, sex ratio, SBP, DBP and WHR between Xinjiang Uygur T2DM group and Xinjiang Uygur non-DM group (P0.05). Compared with non-DM group, the mRNA expression level of FOSL2 gene in Uygur T2DM group was significantly lower than that in non-DM group of Xinjiang Uygur nationality (2.456 卤0.512C0.996 卤0.159 P0.01). 涓庢柊鐤嗙淮鍚惧皵鏃忛潪DM鐥呯粍鐩告瘮,鏂扮枂缁村惥灏旀棌T2DM缁勬偅鑰匜OSL2鍩哄洜CPG Unit3(CPG_3)(0.016卤0.004,0.030卤0.003;P0.01),CPG Unit4(CPG_4.5)(0.065卤0.006,0.095卤0.007;P0.05),CPG Unit5(CPG_6.7)(0.002卤0.001,0.014卤0.002;P0.01),CPG Unit6(CPG_8)(0.004卤0.001,0.023卤0.003;P0.01),CPG Unit8(CPG_11)(0.002卤0.001,0.029卤0.003;P0.01),CPG Unit9(CPG_12.13.14)(0.092卤0.004,0.119卤0.003;P0.01),CPG Unit10(CPG_15.16.17)(0.008卤0.002,0.019卤0.001;P0.01)DNA鐨勭敳鍩哄寲鐜囧潎杈冮珮;4. In Xinjiang Uygur T2DM group, the average DNA methylation rate of FOSL2 gene was taken as the dependent variable, the age, height, weight, waist circumference, hip circumference of WHRBMIand pulse rate of SBPNDBPFPPFPPFPGFG, HbA1cTCnTCnTGG / LDLHDL were used as independent variables. The results showed that the patients' height, body weight, waist circumference and hip circumference were determined by multivariate linear regression analysis, and the results showed that the patients' height, weight, waist circumference, hip circumference, etc. Body weight, BMI, pulse rate, SBP, FPGG, HB A 1c entered the regression equation. The regression equation was: yyyong -1.521 0.007 (height) -0.006 (body weight) 0.018 (BMI) 0.001 (pulse rate) 0.001 (SBP) -0.003 (FPG) 0.004 (HbA1c). Conclusion: 1. FOSL2 gene may be associated with T2DM. obesity and abnormal metabolism of glucose and lipid. 2. Hypermethylation of DNA of FOSL2 gene may lead to down-regulation of mRNA expression level, and participate in the occurrence and development of T2DM in Xinjiang Uygur nationality.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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