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Polymorphisms of Glucose Transporter Genes Associated with Type II Diabetes

与II型糖尿病相关的葡萄糖转运蛋白基因多态性

基本信息

批准号：
01570645
负责人：
KAKU Kohei
金额：
$ 1.34万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570645/
关键词：
glucose transporter gene RFLPs type II diabetes (NIDDM)GLUT-1 GLUT-2 GLUT-4 遺伝子ハプロタイプ

项目摘要

To assess the contribution of the glucose transporter genes to the inherited susceptibility to Non-insulin Dependent Diabetes Mellitus (NIDDM, type II), restriction fragment length polymorphisms (RFLPs) at GLUT-1 (HepG2/erythrocyte), GLUT-2 (liver/pancreas), and GLUT-4 (muscle/adipocyte) loci were analyzes. Four RFLPs were observed at GLUT-1 locus, including BgIII, TaqI, XbaI and PstI sites. Pairwise analysis and extended haplotypes revealed the random association between the polymorphic sites (linkage equilibrium). The variability of the RFLPs was determined in four different populations (Whites, American Blacks, Pima Indians, Japanese). The frequency of BgIII RFLP was extremely low in White chromosomes. Both the TagI and PstI polymorphisms were relatively infrequent in all populations and were only slightly informative.Four polymorphic sites were observed at GLUT-2 locus, including EcoRI, HaeIII, and two TaqI RFLPs. Each site was confirmed by multiple dihestion with excess enzyme and … More by ingeritence in families. EcoRI and HaeIII RFLPs appear to be due to an insertion and/or deletion of 200 bp of DNA at same locati on. The linkage disequlibrium between each RFLP was assessed by pairwise analysis. The estimated haplotype frequencies for each pair of RFLPs differed from the frequency predicted if the polymorphisms were randomly associated. Thus significant linkage disequlibrium between sites was suggested. It was also suggested that these RFLPs could be in linkage disequlibrium with mutations at this locus if they exists. The frequencies of RFLPs at GLUT-2 locus were different among the racial groups. The extremely low frequency of RFLPs were observed in Japanese. This fact requires us to find a new valuable RFLP in this population. KpnI polymorphisms was observed at GLUT-4 locus. There was no difference in the frequency of this RFLP among the racial groups.The allelic, genotypic, and haplotypic frequencies of the DNA polymorphisms at these three loci in NIDDM subjects did not differ from the frequencies in nondiabetic subjects as far as analyzed in a small number of subjects including Japanese. Analysis for extended haplotypes including overall genetic loci (GLUT-1, -2 & -4) in each individual and family linkage analysis should be completed to further assess the contribution of these loci to the genetic susceptibility of NIDDM. Less

为了评估葡萄糖转运蛋白基因对非胰岛素依赖型糖尿病（NIDDM，II型）遗传易感性的贡献，分析了GLUT-1（HepG 2/红细胞）、GLUT-2（肝脏/胰腺）和GLUT-4（肌肉/脂肪细胞）位点的限制性片段长度多态性（RFLP）。在GLUT-1基因座上观察到4个RFLPs，分别为BgIII、TaqI、XbaI和PstI位点。成对分析和扩展单倍型揭示了多态位点之间的随机关联（连锁平衡）。在四个不同的人群（白人，美国黑人，皮马印第安人，日本）的RFLPs的变异性进行了测定。Bg Ⅲ RFLP在白色染色体上的频率极低。在GLUT-2基因座上共观察到4个多态位点，包括EcoR Ⅰ、Hae Ⅲ和2个TaqI RFLPs。每个位点通过用过量的酶进行多次变性来确认， ...更多信息在家庭中的继承权。EcoRI和Hae Ⅲ RFLP可能是由于同一位点上200 bp的DNA插入和/或缺失所致，通过两两分析，确定了各RFLP之间的连锁不平衡。每对RFLP的估计单倍型频率与多态性随机相关时的预测频率不同。因此，位点之间存在显著的连锁不平衡。这些RFLPs可能与该位点的突变存在连锁不平衡。GLUT-2基因座上的RFLPs频率在不同人种间存在差异。日本人的RFLP频率极低。这一事实要求我们在该群体中寻找新的有价值的RFLP。在GLUT-4位点上观察到Kpn I多态性。在包括日本人在内的少数受试者中，NIDDM受试者这三个位点的DNA多态性的等位基因、基因型和单倍型频率与非糖尿病受试者的频率没有差异。进一步分析这些基因座对NIDDM遗传易感性的贡献，需要对每个个体进行包括GLUT-1、GLUT-2和GLUT-4在内的扩展单倍型分析和家系连锁分析。少