TLR2固有免疫通路基因多态性与2型糖尿病血管病变遗传易感性的关联研究

发布时间：2018-07-09 13:29

  本文选题：2型糖尿病 + toll样受体　； 参考：《暨南大学》2015年硕士论文

【摘要】：1.研究目的2型糖尿病(Type 2 diabetes mellitus,T2DM)是一种慢性炎症性代谢性疾病,对机体多个器官可造成损害,但其具体发病机制仍不明确。TLRs(Toll-like receptor)细胞信号通路参与多个炎症反应,其介导的NF-κB通路在糖尿病的发生、发展过程中起重要作用,然而其与T2DM血管病变的发病关联尚不清楚。本研究通过病例对照研究设计方法,探讨在中国单纯T2DM人群中TLR2细胞信号通路中关键基因TLR2、TRAF3和NLRX1基因的遗传变异与T2DM血管并发症的关联。2.研究方法(1)采用病例对照研究设计,共设立3个比较组:单纯T2DM与T2DM伴微血管并发症、单纯T2DM与T2DM伴大血管并发症以及单纯T2DM与T2DM合并微血管大血管并发症。其中,单纯T2DM有120例、T2DM伴微血管病变176例、T2DM伴大血管病变51例、T2DM伴微血管大血管病变105例。(2)收集4组病人的基本临床资料,具体包括性别、年龄、体重指数(BMI)、家族史、吸烟史、饮酒史、糖化血红蛋白、总胆固醇、总甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇。(3)利用生物数据库筛选TLR2基因、TRAF3基因和NLRX1基因的SNP位点。(4)采用统计学分析比较单纯T2DM病人TLR2基因、TRAF3基因和NLRX1基因的多态性与其发生血管并发症的相关性。3.研究结果(1)所选的3个基因共筛选了9个SNP位点,他们分别是:TLR2基因的rs1898830位点、rs4696480位点、rs3804099位点和rs3804100位点;TRAF3基因的rs2144826位点、12435483位点和rs3803286位点;NLRX1基因的rs10790286和rs561830位点。(2)经校正年龄、性别和BMI因素后,在NLRX1基因的rs561830位点,与携带CC基因型相比,单纯2型糖尿病患者携带TT基因型其患糖尿病微血管并发症的风险增加120%(OR=2.20,95%CI:1.02-4.74,p=0.044)。TLR2基因rs1898830位点的AA基因型与AG+GG基因型相比,发生大血管病变的风险增加了146%(OR=2.46,95%CI:1.03-5.86,p=0.043)。TLR2基因rs1898830位点的AA基因型与GG基因型相比,发生微血管大血管病变的风险增加了228%(OR=3.28,95%CI:1.23-8.79,p=0.018);与携带AG+GG基因型相比,患微血管大血管的风险增加了128%(OR=2.28.95%CI:1.16-4.46,p=0.017)。在TLR2基因的rs4696480位点上,携带AA基因型的单纯T2DM患者比携带TT基因型的患者患微血管大血管并发症的风险增加256%(OR=3.56,95%CI:1.35-9.40,p=0.011)。与基因型AA+AT的患者相比,其患微血管大血管的风险增加了156%(OR=2.56,95%CI:1.32-4.98,p=0.006)。在TRAF3基因的rs2144826位点,携带AA基因型的患者发生两种并发症的风险是携带GG基因型患者罹患的16.6倍(OR=16.60,95%CI:1.52-181.11,p=0.021);携带AA基因型的患者患两种并发症的风险是携带AG+GG基因型的患者的15.89倍(OR=15.89,95%CI:1.47-171.42,p=0.023)。在NLRX1基因的rs561830位点上,单纯2型糖尿病患者携带TT基因型其患微血管大血管并发症的风险比患者携带CC基因型增加239%(OR=3.39,95%CI:1.28-8.99,p=0.014);患者携带TC基因型,则其患并发症的风险比携带CC基因型增加166%(OR=2.66,95%CI:1.30-5.44,p=0.007);患者携带TT+TC基因型,与CC基因型相比较,其患微血管大血管并发症的风险增加了182%(OR=2.82,95%CI:1.43-5.58,p=0.003)。4.研究结论TLR2基因、TRAF3基因和NLRX1基因可能会增加T2DM患者患血管并发症的易感性,其功能尚需要进一步验证。
[Abstract]:1. research objective type 2 diabetes mellitus (Type 2 diabetes mellitus, T2DM) is a chronic inflammatory metabolic disease, which can cause damage to multiple organs of the body, but its specific pathogenesis is still not clear about the.TLRs (Toll-like receptor) cell signaling pathway involved in multiple inflammatory reactions, and its mediated NF- kappa B pathway in the development of diabetes and development process It plays an important role, however, it is not clear that its association with T2DM vascular disease is not clear. In this study, a case-control study design method was used to investigate the genetic variation of the TLR2 cell signaling pathway of the TLR2 cells in Chinese T2DM population, the genetic variation of the TRAF3 and NLRX1 genes and the.2. research method of T2DM vasculopathy (1) a case-control study. A total of 3 comparative groups were set up: simple T2DM and T2DM with microvascular complications, simple T2DM and T2DM with large vascular complications and simple T2DM and T2DM complicated with microvascular complications. Among them, there were only 120 cases of T2DM, 176 cases of T2DM with microvascular lesions, 51 cases of T2DM accompanied by large vascular lesions, 105 cases of T2DM with microvascular macrovascular lesions. (2) (2) The basic clinical data of 4 groups of patients, including sex, age, body mass index (BMI), family history, smoking history, drinking history, glycosylated hemoglobin, total cholesterol, total triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol. (3) the screening of TLR2, TRAF3 and NLRX1 genes using the raw material database (4) (4) Statistical analysis was used to compare the TLR2, TRAF3, and NLRX1 gene polymorphisms of T2DM patients with the correlation.3. study of vascular complications (1) the selected 3 genes selected 9 SNP loci, they were the rs1898830 site, rs4696480, rs3804099 and rs3804100 loci of the TLR2 gene, and the TRAF3 gene. Rs2144826 loci, 12435483 loci and rs3803286 loci; rs10790286 and rs561830 loci of the NLRX1 gene. (2) after correction of age, sex, and BMI factors, the risk of carrying a TT genotype with the TT genotype in simple type 2 diabetic patients increased by 120% (OR=2.20,95%CI) at the rs561830 site of the NLRX1 gene compared with those with the CC genotype. 1.02-4.74, p=0.044) the AA genotypes at the rs1898830 locus of the.TLR2 gene, compared with the AG+GG genotype, increased the risk of large vascular lesions by 146% (OR=2.46,95%CI:1.03-5.86, p=0.043).TLR2 gene rs1898830 AA genotype compared with the GG genotypes, and increased the risk of microvascular macroangiopathy by 228%. 0.018): compared with the AG+GG genotype, the risk of microvascular large vessels increased by 128% (OR=2.28.95%CI:1.16-4.46, p=0.017). At the rs4696480 site of the TLR2 gene, the risk of microvascular concomatation with the AA genotype was 256% (OR=3.56,95%CI:1.35-9.40, p=0.011) more than those with the TT genotype. The risk of microvascular large vessels increased by 156% (OR=2.56,95%CI:1.32-4.98, p=0.006) compared with those with genotype AA+AT. At the rs2144826 locus of the TRAF3 gene, the risk of two complications in the patients carrying the AA genotype was 16.6 times the risk of carrying the GG genotype (OR=16.60,95%CI:1.52-181.11, p=0.021); and the AA genotype was carried. The risk of two complications was 15.89 times (OR=15.89,95%CI:1.47-171.42, p=0.023) in the patients with the AG+GG genotype. At the rs561830 site of the NLRX1 gene, the risk of carrying the TT genotypes in the simple type 2 diabetes mellitus patients with the microvascular macrovascular complications increased by 239% (OR=3.39,95%CI:1.28-8.99, p=0) than the patients carrying the CC genotype. .014); patients carrying TC genotypes increased the risk of complications by 166% (OR=2.66,95%CI:1.30-5.44, p=0.007) than carrying CC genotypes, and patients carrying TT+TC genotypes, compared with the CC genotype, increased the risk of microvascular complications by 182% (OR= 2.82,95%CI:1.43-5.58, p=0.003).4. study of TLR2 genes. And NLRX1 gene may increase the susceptibility of T2DM patients to vascular complications, and its function needs further verification.
【学位授予单位】：暨南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.2
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本文编号：2109515