Smad3基因和ACE基因与2型糖尿病患者糖尿病视网膜病变的关系的初步探讨

发布时间：2018-01-20 15:37

本文关键词： 糖尿病性视网膜病变单核苷酸多态性 Smad3基因 ACE基因基质辅助激光解吸电离飞行时间质谱　出处：《天津医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的：糖尿病视网膜病变(DR)的发病受多种基因的影响,对DR易感基因的多态性的研究,有助于我们深入了解其发病机制；候选基因研究在DR的易感基因的研究中占有重要地位。 TGF-β/Smad信号转导通路在DR的发生发展中起着重要作用,Smad3是该信号转导通路中的最重要的介质,既往的TGF-β/Smad信号转导通路与DR的相关性研究多集中于细胞因子信号转导通路的层面上,我们以Smad3基因作为DR的候选基因之一在基因层面进行研究；血管紧张素转换酶(ACE)在肾素-血管紧张素系统(RAS)中起着枢纽作用,RAS也通过各种途径参与了DR的发生发展,在基因层面上,既往对其16内含子内插入／缺失(I/D)多态性与DR的相关性已有大量研究,但对其SNP位点还鲜有报道,我们也将ACE基因作为DR的候选基因之一,对其SNP位点与DR的相关性进行研究。因此,本研究将Smad3基因与ACE基因作为DR的候选基因,初步探讨Smad3基因rs1498506、rs12102171位点与ACE基因rs4353位点基因多态性与中国汉族人2型糖尿病患者DR的相关性。方法：本研究选取久居天津、彼此之间无血缘关系的汉族2型糖尿病患者共412名,其中DR患者258名(NPDR患者158名,PDR患者100名),对照组154名(均为病程长于10年的未罹患DR和DN的患者)。取空腹外周血标本,血清用于生物化学指标检测,检测空腹血糖(FPG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、尿素氮(BUN)、肌酐(SCR)、尿酸(UA)；全血用于提取基因组DNA。提取并纯化的基因组DNA应用基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOF-MS),对Smad3基因rs1498506、rs12102171位点与ACE基因rs4353位点进行基因分型,利用SPSS和PLINK软件对各SNP位点与一般临床生物化学指标的关联性,及进一步的与DR及PDR之间的关联性进行分析。结果：(1)各SNP位点与DR及PDR的二分变量关联分析。Smad3基因rs1498506和ACE基因rs4353位点与DR均无相关性(P=0.69及P=0.96),Smad3基因rs12102171位点与DR具有相关性(P=0.03)；Smad3基因rs1498506和ACE基因rs4353位点与PDR亦均无相关性(P=0.64及P=0.79),Smad3基因rs12102171位点与PDR具有相关性(P=0.02)。 (2)各SNP位点与临床生物化学指标的数量性状关联分析。Smad3基因rs1498506、rs12102171与ACE基因rs4353三个位点在以性别分组并分别经过年龄调整、体质指数(BMI)调整、病程调整之后,均与FPG、HbA1c、TC、TG、 BUN、SCR、UA等临床生物化学指标没有相关性(P0.05);在去除极端值数据后,三个SNP位点与FPG、HbA1c、TC、TG、BUN、SCR、UA等临床生物化学指标均没有相关性(P0.05)。结论：在中国汉族人群中,Smad3基因rs1498506、ACE基因rs4353位点与DR及PDR均无相关性;Smad3基因rs12102171位点与DR及PDR均具有相关性,且T等位基因是DR和PDR的危险因子。
[Abstract]:Objective: the pathogenesis of diabetic retinopathy (Dr) is affected by many genes. The study on the polymorphism of Dr susceptibility gene is helpful for us to understand the pathogenesis of Dr. Candidate genes play an important role in the study of Dr susceptibility genes. TGF- 尾 / Smad signal transduction pathway plays an important role in the development of Dr. Smad3 is the most important medium in the signal transduction pathway. Previous studies on the correlation between TGF- 尾 / Smad signal transduction pathway and Dr were focused on cytokine signal transduction pathway. We used Smad3 gene as one of the candidate genes for Dr. Angiotensin converting enzyme (ACE) plays a pivotal role in the renin-angiotensin system (Ras). Ras is also involved in the development of Dr through various ways. The association of intron 16 insertion / deletion I / D polymorphism with Dr has been extensively studied, but the SNP locus has not been reported. We also used ACE gene as one of the candidate genes for Dr, and studied the correlation between Dr and SNP locus. Therefore, in this study, Smad3 gene and ACE gene were considered as candidate genes for Dr, and Smad3 gene rs1498506 was preliminarily discussed. The relationship between the polymorphism of rs12102171 locus and rs4353 locus of ACE gene and Dr of type 2 diabetes in Chinese Han nationality. Methods: a total of 412 Han patients with type 2 diabetes mellitus (T2DM) living in Tianjin for a long time were enrolled in this study, including 258 patients with Dr and 158 patients with NPDR. The fasting peripheral blood samples were collected from 100 patients with PDR and 154 patients from the control group (all patients with longer course than 10 years). The serum was used to detect biochemical indexes. Fasting blood glucose (FPG), glycosylated hemoglobin (HbA1cN), total cholesterol (TC), triglyceride (TGN), bun (bun), creatinine (SCR) and uric acid (UAA) were detected. Whole blood was used to extract genomic DNA. The extracted and purified genomic DNA was extracted and purified by MALDI-TOF-MSusing matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The loci of Smad3 gene rs1498506 rs12102171 and ACE gene rs4353 were genotyped. SPSS and PLINK software were used to analyze the relationship between SNP loci and general clinical biochemical indexes, as well as with Dr and PDR. Results there was no correlation between Smad3 gene rs1498506 and ACE gene rs4353 locus and Dr (P < 0.05). P0. 69 and P0. 96). The rs12102171 locus of Smad3 gene was correlated with Dr. There was no correlation between the rs4353 locus of Smad3 gene rs1498506 and ACE gene and PDR. The rs12102171 locus of Smad3 gene was correlated with PDR. (2) correlation analysis of quantitative traits between each SNP locus and clinical biochemical indexes. The rs1498506 of Smad3 gene was analyzed. The three rs4353 loci of rs12102171 and ACE gene were grouped by sex and adjusted by age and body mass index (BMI) respectively. After the course of disease was adjusted, they were all associated with FPG. There was no correlation between the clinical biochemical indexes such as HBA _ 1C _ (TCN) TG, BUNA SCRU UA and so on (P 0.05). After the extreme value data were removed, there was no correlation between the three SNP loci and the clinical biochemical indexes such as TGN, TGN, TGN, SCRU, etc. Conclusion: there is no correlation between the rs4353 locus of Smad3 gene rs1498506ACE and Dr and PDR in Chinese Han population. The rs12102171 locus of Smad3 gene was correlated with Dr and PDR, and T allele was the risk factor of Dr and PDR.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R774.1;R587.2

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