本文選題：2型糖尿病 + toll樣受體��； 參考：《暨南大學(xué)》2015年碩士論文

【摘要】：1.研究目的2型糖尿病(Type 2 diabetes mellitus,T2DM)是一種慢性炎癥性代謝性疾病,對(duì)機(jī)體多個(gè)器官可造成損害,但其具體發(fā)病機(jī)制仍不明確。TLRs(Toll-like receptor)細(xì)胞信號(hào)通路參與多個(gè)炎癥反應(yīng),其介導(dǎo)的NF-κB通路在糖尿病的發(fā)生、發(fā)展過(guò)程中起重要作用,然而其與T2DM血管病變的發(fā)病關(guān)聯(lián)尚不清楚。本研究通過(guò)病例對(duì)照研究設(shè)計(jì)方法,探討在中國(guó)單純T2DM人群中TLR2細(xì)胞信號(hào)通路中關(guān)鍵基因TLR2、TRAF3和NLRX1基因的遺傳變異與T2DM血管并發(fā)癥的關(guān)聯(lián)。2.研究方法(1)采用病例對(duì)照研究設(shè)計(jì),共設(shè)立3個(gè)比較組:單純T2DM與T2DM伴微血管并發(fā)癥、單純T2DM與T2DM伴大血管并發(fā)癥以及單純T2DM與T2DM合并微血管大血管并發(fā)癥。其中,單純T2DM有120例、T2DM伴微血管病變176例、T2DM伴大血管病變51例、T2DM伴微血管大血管病變105例。(2)收集4組病人的基本臨床資料,具體包括性別、年齡、體重指數(shù)(BMI)、家族史、吸煙史、飲酒史、糖化血紅蛋白、總膽固醇、總甘油三酯、高密度脂蛋白膽固醇、低密度脂蛋白膽固醇。(3)利用生物數(shù)據(jù)庫(kù)篩選TLR2基因、TRAF3基因和NLRX1基因的SNP位點(diǎn)。(4)采用統(tǒng)計(jì)學(xué)分析比較單純T2DM病人TLR2基因、TRAF3基因和NLRX1基因的多態(tài)性與其發(fā)生血管并發(fā)癥的相關(guān)性。3.研究結(jié)果(1)所選的3個(gè)基因共篩選了9個(gè)SNP位點(diǎn),他們分別是:TLR2基因的rs1898830位點(diǎn)、rs4696480位點(diǎn)、rs3804099位點(diǎn)和rs3804100位點(diǎn);TRAF3基因的rs2144826位點(diǎn)、12435483位點(diǎn)和rs3803286位點(diǎn);NLRX1基因的rs10790286和rs561830位點(diǎn)。(2)經(jīng)校正年齡、性別和BMI因素后,在NLRX1基因的rs561830位點(diǎn),與攜帶CC基因型相比,單純2型糖尿病患者攜帶TT基因型其患糖尿病微血管并發(fā)癥的風(fēng)險(xiǎn)增加120%(OR=2.20,95%CI:1.02-4.74,p=0.044)。TLR2基因rs1898830位點(diǎn)的AA基因型與AG+GG基因型相比,發(fā)生大血管病變的風(fēng)險(xiǎn)增加了146%(OR=2.46,95%CI:1.03-5.86,p=0.043)。TLR2基因rs1898830位點(diǎn)的AA基因型與GG基因型相比,發(fā)生微血管大血管病變的風(fēng)險(xiǎn)增加了228%(OR=3.28,95%CI:1.23-8.79,p=0.018);與攜帶AG+GG基因型相比,患微血管大血管的風(fēng)險(xiǎn)增加了128%(OR=2.28.95%CI:1.16-4.46,p=0.017)。在TLR2基因的rs4696480位點(diǎn)上,攜帶AA基因型的單純T2DM患者比攜帶TT基因型的患者患微血管大血管并發(fā)癥的風(fēng)險(xiǎn)增加256%(OR=3.56,95%CI:1.35-9.40,p=0.011)。與基因型AA+AT的患者相比,其患微血管大血管的風(fēng)險(xiǎn)增加了156%(OR=2.56,95%CI:1.32-4.98,p=0.006)。在TRAF3基因的rs2144826位點(diǎn),攜帶AA基因型的患者發(fā)生兩種并發(fā)癥的風(fēng)險(xiǎn)是攜帶GG基因型患者罹患的16.6倍(OR=16.60,95%CI:1.52-181.11,p=0.021);攜帶AA基因型的患者患兩種并發(fā)癥的風(fēng)險(xiǎn)是攜帶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位點(diǎn)上,單純2型糖尿病患者攜帶TT基因型其患微血管大血管并發(fā)癥的風(fēng)險(xiǎn)比患者攜帶CC基因型增加239%(OR=3.39,95%CI:1.28-8.99,p=0.014);患者攜帶TC基因型,則其患并發(fā)癥的風(fēng)險(xiǎn)比攜帶CC基因型增加166%(OR=2.66,95%CI:1.30-5.44,p=0.007);患者攜帶TT+TC基因型,與CC基因型相比較,其患微血管大血管并發(fā)癥的風(fēng)險(xiǎn)增加了182%(OR=2.82,95%CI:1.43-5.58,p=0.003)。4.研究結(jié)論TLR2基因、TRAF3基因和NLRX1基因可能會(huì)增加T2DM患者患血管并發(fā)癥的易感性,其功能尚需要進(jìn)一步驗(yàn)證。
[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.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R587.2
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本文編號(hào)：2109515