胰岛素样生长因子1启动子区基因多态性与胰岛素敏感性研究

发布时间：2018-04-04 05:37

  本文选题：胰岛素样生长因子1　切入点：微卫星　出处：《天津医科大学》2017年硕士论文

【摘要】：胰岛素样生长因子1(insulin-like growth factor 1,IGF1)是一种肽类激素,在细胞生长、增殖以及凋亡过程中发挥重要作用;同时,IGF1也具有胰岛素样的代谢效应,在维持血糖稳态和调节胰岛素敏感性的过程中发挥重要作用。胰岛素抵抗是各种原因导致的胰岛素促葡萄糖摄取和利用效率下降,机体代偿性分泌过多胰岛素产生高胰岛素血症,以维持血糖的稳定。近年来,多项研究表明IGF1在胰岛素抵抗中扮演着重要的角色,然而,关于IGF1基因启动子区CA微卫星和单核苷酸多态性与胰岛素敏感性相关关系的研究结论并不一致。目的:本研究旨在探讨IGF1基因启动子区CA微卫星、SNP rs35767,rs5742612,rs2288377基因型以及三个SNP位点联合CA微卫星单倍型与胰岛素敏感性和胰岛素分泌相关指标之间的关系。方法:研究纳入了389例2型糖尿病住院患者,采集空腹静脉血,检测血糖、胰岛素、C肽、IGF1、糖化血红蛋白以及血脂指标;予所有受试者75g口服葡萄糖耐量试验,采集60分钟及120分钟静脉血,分别检测血清葡萄糖、胰岛素和C肽;外周血白细胞提取基因组DNA,并进行CA微卫星和rs35767,rs5742612,rs2288377多态性分型。利用协方差分析(一般线性模型)比较研究对象不同基因型或单倍型间临床和实验室指标的差异,利用多元线性回归分析研究对象基因型或单倍型与其代谢相关因素的相关关系。结果:回归分析表明,在调整了性别、年龄和身体质量指数后,rs5742612位点C等位基因与胰岛素敏感性降低(HOMA-S,β=-0.131,P=0.008;空腹胰岛素,β=0.022,P=0.006)以及胰岛素分泌增高(HOMA-B,β=0.099,P=0.008;insulin AUC,β=0.112,P=0.012)有关;rs2288377位点A等位基因与胰岛素敏感性降低(HOMA-S,β=-0.159,P=0.001;空腹胰岛素,β=0.143,P=0.001)和胰岛素分泌增高(HOMA-B,β=0.114,P=0.017;insulin AUC,β=0.042,P=0.002)有关;SNP单倍型与循环IGF1水平有关,在调整了性别、年龄、身体质量指数之后,β=0.026,P=0.042。CA微卫星、rs35767多态性、SNP单倍型以及SNPCA单倍型与胰岛素敏感性或胰岛素分泌相关代谢指标关联性分析差异无统计学意义;rs5742612和rs2288377位点基因型与IGF1浓度无统计学相关性。结论:SNP rs5742612和rs2288377基因型与胰岛素敏感性和胰岛素分泌指标显著相关:与rs5742612位点TT基因型携带者相比,C等位基因携带者胰岛素敏感性较低,胰岛素分泌较高;与rs2288377位点TT基因型携带者相比,A等位基因携带者胰岛素敏感性较低,胰岛素分泌较高。IGF1基因启动子区CA微卫星和SNP rs35767基因型以及SNP、SNPCA单倍型与胰岛素敏感性和胰岛素分泌无关。
[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,骞撮緞鍜岃韩浣撹川閲忔寚鏁板悗,rs5742612浣嶇偣C绛変綅鍩哄洜涓庤儼宀涚礌鏁忔劅鎬ч檷浣，

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