胰岛素启动子因子1基因突变与上海地区糖尿病发病的关联

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目的:对上海地区2型糖尿病患者、特发性1型糖尿病患者及健康者进行胰岛素启动子因子1基因序列筛查,探讨该基因在糖尿病发病中的作用。方法:①选择2002-05/2003-12上海交通大学附属第一人民医院内分泌科住院2型糖尿病及特发性1型糖尿病患者。2型糖尿病患者201例(2型糖尿病组),男94例,女107例;特发性1型糖尿病患者4例(特发性1型糖尿病组),男3例,女1例。纳入同期本院内分泌门诊体检健康者100例为对照组,男67例,女33例。均自愿接受相关检查,并对实验目的知情同意。②测定血生化学指标及与糖尿病发病相关抗体。对胰岛素启动子因子1基因的两个外显子序列(包括编码区及侧翼区)进行聚合酶链反应扩增,聚合酶链反应产物经纯化后,经ABI377DNA全自动测序仪对所有聚合酶链反应产物直接测序。发现突变后用特异性限制性内切酶对突变位点进行酶切,验证突变。③正态分布数据以x±s表示,偏态分布数据用M表示,C肽呈偏态分布将其转换为以10为底的对数后呈正态分布。结果:2型糖尿病患者201例,特发性1型糖尿病患者4例,健康者100例均进入结果分析。2型糖尿病组及对照组中均未发现胰岛素启动子因子1基因突变。特发性1型糖尿病组中发现1例P239Q(CCG-CAG)杂合突变,该聚合酶链反应产物可被PstⅠ部分酶切,所切的2个片段大小分别为347和252bp,与预测相吻合。结论:①胰岛素启动子因子1基因不是上海地区2型糖尿病发病的主要易感基因。②4例特发性1型糖尿病中发现1例P239Q(CCG-CAG)突变,今后需扩大样本量及对先证者作家系调查,以探讨胰岛素启动子因子1基因突变是否与特发性1型糖尿病早期胰岛功能衰竭有关,为今后对特发性1型糖尿病的病因研究开拓思路。 OBJECTIVE: To screen the insulin promoter 1 gene sequence of type 2 diabetes mellitus, idiopathic type 1 diabetes mellitus and healthy people in Shanghai to investigate the role of this gene in the pathogenesis of diabetes mellitus. Methods: ①The inpatients with type 2 diabetes and idiopathic type 1 diabetes in Department of Endocrinology, First People’s Hospital Affiliated to Shanghai Jiao Tong University from May 2002 to December 2003 were selected. There were 201 patients with type 2 diabetes (type 2 diabetes), 94 males and 107 females, 4 idiopathic type 1 diabetic patients (idiopathic type 1 diabetes mellitus), 3 males and 1 female. Included in the same period endocrine clinic physical examination in 100 cases as control group, 67 males and 33 females. Voluntarily accept the relevant inspection, and informed consent for the purpose of the experiment. ② Determination of blood biochemical indicators and the incidence of diabetes-related antibodies. Two exon sequences (including coding region and flanking region) of insulin promoter factor 1 gene were amplified by polymerase chain reaction (PCR). After purified by PCR, all the polymerase chain The reaction product is directly sequenced. After the mutation was found, the mutation site was digested with specific restriction endonuclease to verify the mutation. ③ normal distribution data to x ± s, said the skewed distribution data with M, C-peptide was skewed distribution of its conversion to a base-10 logarithmic normal distribution. Results: 201 patients with type 2 diabetes mellitus, 4 patients with idiopathic type 1 diabetes mellitus, and 100 healthy subjects were involved in the result analysis. Insulin promoter 1 gene mutation was not found in type 2 diabetes mellitus group and control group. One case of P239Q (CCG-CAG) heterozygous mutation was found in idiopathic type 1 diabetes mellitus. The PCR products were partially digested by PstⅠ. The sizes of the two fragments were 347 and 252 bp, respectively, Anastomosis. Conclusion: (1) Insulin promoter factor 1 gene is not the major susceptibility gene in type 2 diabetes in Shanghai. ② One case of P239Q (CCG-CAG) mutation was found in 4 idiopathic type 1 diabetes mellitus, and the sample size and the investigation of the proband’s author were needed in order to find out whether the mutation of insulin promoter 1 is associated with idiopathic type 1 Diabetes early pancreatic islet failure, for future research on the etiology of idiopathic type 1 diabetes open up ideas.
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