本文選題：胰島素樣生長因子1　切入點(diǎn)：微衛(wèi)星　出處：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：胰島素樣生長因子1(insulin-like growth factor 1,IGF1)是一種肽類激素,在細(xì)胞生長、增殖以及凋亡過程中發(fā)揮重要作用;同時,IGF1也具有胰島素樣的代謝效應(yīng),在維持血糖穩(wěn)態(tài)和調(diào)節(jié)胰島素敏感性的過程中發(fā)揮重要作用。胰島素抵抗是各種原因?qū)е碌囊葝u素促葡萄糖攝取和利用效率下降,機(jī)體代償性分泌過多胰島素產(chǎn)生高胰島素血癥,以維持血糖的穩(wěn)定。近年來,多項研究表明IGF1在胰島素抵抗中扮演著重要的角色,然而,關(guān)于IGF1基因啟動子區(qū)CA微衛(wèi)星和單核苷酸多態(tài)性與胰島素敏感性相關(guān)關(guān)系的研究結(jié)論并不一致。目的:本研究旨在探討IGF1基因啟動子區(qū)CA微衛(wèi)星、SNP rs35767,rs5742612,rs2288377基因型以及三個SNP位點(diǎn)聯(lián)合CA微衛(wèi)星單倍型與胰島素敏感性和胰島素分泌相關(guān)指標(biāo)之間的關(guān)系。方法:研究納入了389例2型糖尿病住院患者,采集空腹靜脈血,檢測血糖、胰島素、C肽、IGF1、糖化血紅蛋白以及血脂指標(biāo);予所有受試者75g口服葡萄糖耐量試驗(yàn),采集60分鐘及120分鐘靜脈血,分別檢測血清葡萄糖、胰島素和C肽;外周血白細(xì)胞提取基因組DNA,并進(jìn)行CA微衛(wèi)星和rs35767,rs5742612,rs2288377多態(tài)性分型。利用協(xié)方差分析(一般線性模型)比較研究對象不同基因型或單倍型間臨床和實(shí)驗(yàn)室指標(biāo)的差異,利用多元線性回歸分析研究對象基因型或單倍型與其代謝相關(guān)因素的相關(guān)關(guān)系。結(jié)果:回歸分析表明,在調(diào)整了性別、年齡和身體質(zhì)量指數(shù)后,rs5742612位點(diǎn)C等位基因與胰島素敏感性降低(HOMA-S,β=-0.131,P=0.008;空腹胰島素,β=0.022,P=0.006)以及胰島素分泌增高(HOMA-B,β=0.099,P=0.008;insulin AUC,β=0.112,P=0.012)有關(guān);rs2288377位點(diǎn)A等位基因與胰島素敏感性降低(HOMA-S,β=-0.159,P=0.001;空腹胰島素,β=0.143,P=0.001)和胰島素分泌增高(HOMA-B,β=0.114,P=0.017;insulin AUC,β=0.042,P=0.002)有關(guān);SNP單倍型與循環(huán)IGF1水平有關(guān),在調(diào)整了性別、年齡、身體質(zhì)量指數(shù)之后,β=0.026,P=0.042。CA微衛(wèi)星、rs35767多態(tài)性、SNP單倍型以及SNPCA單倍型與胰島素敏感性或胰島素分泌相關(guān)代謝指標(biāo)關(guān)聯(lián)性分析差異無統(tǒng)計學(xué)意義;rs5742612和rs2288377位點(diǎn)基因型與IGF1濃度無統(tǒng)計學(xué)相關(guān)性。結(jié)論:SNP rs5742612和rs2288377基因型與胰島素敏感性和胰島素分泌指標(biāo)顯著相關(guān):與rs5742612位點(diǎn)TT基因型攜帶者相比,C等位基因攜帶者胰島素敏感性較低,胰島素分泌較高;與rs2288377位點(diǎn)TT基因型攜帶者相比,A等位基因攜帶者胰島素敏感性較低,胰島素分泌較高。IGF1基因啟動子區(qū)CA微衛(wèi)星和SNP rs35767基因型以及SNP、SNPCA單倍型與胰島素敏感性和胰島素分泌無關(guān)。
[Abstract]:Insulin-like growth factor (1(insulin-like growth factor 1) is a peptide hormone that plays an important role in cell growth, proliferation and apoptosis.It plays an important role in maintaining blood glucose homeostasis and regulating insulin sensitivity.Insulin resistance is caused by the decrease of glucose uptake and utilization efficiency, and the compensatory secretion of excessive insulin produces hyperinsulinemia in order to maintain the stability of blood glucose.In recent years, many studies have shown that IGF1 plays an important role in insulin resistance. However, the relationship between IGF1 gene promoter CA microsatellite and single nucleotide polymorphism and insulin sensitivity is not consistent.Aim: to investigate the relationship between the genotypes of SNP rs35767 and rs5742612 rs2288377 in the promoter region of IGF1 gene and the insulin sensitivity and insulin secretion of three SNP loci combined with CA microsatellite haplotypes.Methods: a total of 389 inpatients with type 2 diabetes were enrolled in the study. Fasting venous blood was collected, blood glucose, insulin C peptide IGF1, glycosylated hemoglobin and blood lipids were measured, and 75 g oral glucose tolerance test was administered to all subjects.Venous blood samples were collected at 60 and 120 minutes to detect serum glucose, insulin and C-peptide respectively. Genomic DNA was extracted from peripheral white blood cells and genotypes of CA microsatellite and rs35767rs5742612 rs2288377 were carried out.Covariance analysis (general linear model) was used to compare the differences of clinical and laboratory indexes among different genotypes or haplotypes.Multivariate linear regression analysis was used to study the correlation between genotype or haplotype and metabolic factors.Results: regression analysis showed that after adjusting for gender,騫撮緞鍜岃韓浣撹川閲忔寚鏁板悗,rs5742612浣嶇偣C絳変綅鍩哄洜涓庤儼宀涚礌鏁忔劅鎬ч檷浣，

本文編號：1708596