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Analysis of genes involved in the susceptibility to type 2 diabetes

2型糖尿病易感性相关基因分析

基本信息

批准号：
03454517
负责人：
KAKU Kohei
金额：
$ 4.1万
依托单位：
Yamaguchi University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

[1991]1.Study samples and DNA preparation : Genomic DNA was extracted from white blood cells of subjects with NIDDM and nondiabetic subjects (>40 yr of age, no personal history of diabetes mellitus, and a random plasma glucose of <6.7 mM).2.Glucose transporter genes in NIDDM - Population study : Contribution of GLUTI and GLUT4 genes to NIDDM was evalulated using genetic markers. A strong association between (-) allele of Xbal site in GLUTI locus and NIDDM was found, but no difference in allelic frequencies of KpnI site in GLUT4 between NIDDM and nondiabetic subjects was observed.[1992]1.Molecular scanning of the GLUT1 gene : Sequence variations in the gene encoding GLUT1 in NIDDM subjects with (-)allele of XbaI site were qnqlyzed using PCR-SSCP and direct sequaencing. Silent mutations were detected in exon 2,5,7,9, and 10.2.Glucokinase gene in NIDDM - Population study : Allelic frequencies of two microsatelite repeat polymorphisms, GCK1 and GCK2, were analyzed. The Z+4 allele in GCK1was found more frequently in diabetic than in nondiabetic subjects, suggesting a relationship between glucokinase defects and the susceptibility to NIDDM in Japanese population.[1993]1.Molecular scanning of the glucokinase gene : In the conding region, a silet mutation in exon 4 was identified. Sequence variations in the islet promoter(at -282, -194, and -30) and in the liver pomoter (at -258) were identified. The frequencies of the variants did not differ between NIDDM and nondiabetic subjects.2.Analysis of promoter activity of the variants in the islet promoter : To assess the effect of sequence variations in the islet promoter region on promoter activety, the promoter activity was analyzed using the luciferase expression vector transformed into HIT cells. The promoter activity of the variant (G - A at -30) was significantly lowered.

[1991] 1.研究样品和DNA制备：从NIDDM受试者和非糖尿病受试者（年龄>40岁，无糖尿病个人史，随机血浆葡萄糖<6.7 mM）的白色血细胞中提取基因组DNA。2. NIDDM中的葡萄糖转运蛋白基因-群体研究：使用遗传标记评估GLUT 1和GLUT 4基因对NIDDM的贡献。GLUT 4基因Xbal位点的（-）等位基因与NIDDM有显著相关性，而GLUT 4基因KpnI位点的等位基因频率在NIDDM与非糖尿病组间无显著性差异。[1992] 1. GLUT 1基因的分子扫描：采用PCR-SSCP和直接测序技术，对Xba Ⅰ位点（-）等位基因的NIDDM患者进行GLUT 1基因序列分析。在外显子2、5、7、9和10中检测到沉默突变。2.葡萄糖激酶基因与NIDDM人群研究：分析GCK 1和GCK 2两个微卫星重复多态性的等位基因频率。GCK 1 Z+4等位基因在糖尿病患者中的频率高于非糖尿病患者，提示葡萄糖激酶缺陷与日本人群中NIDDM的易感性有关。[1993] 1.葡萄糖激酶基因的分子扫描：在第4外显子的编码区发现了一个silet突变。确定了胰岛启动子（-282、-194和-30）和肝启动子（-258）的序列变异。2.胰岛启动子区变异启动子活性分析：利用转化HIT细胞的荧光素酶表达载体分析胰岛启动子区序列变异对启动子活性的影响。变体（G-A at-30）的启动子活性显著降低。