Polymorphisms of Glucose Transporter Genes Associated with Type II Diabetes

分析GLUT-1(HepG2/红细胞)、GLUT-2(肝/胰腺)和GLUT-4(肌肉/脂肪细胞)基因座的限制性片段长度多态(RFLP)，以探讨葡萄糖转运蛋白基因在非胰岛素依赖型糖尿病(NIDDM)遗传易感性中的作用。在GLUT-1基因座上检测到4个RFLP，包括BgIII、Taqi、XbaI和PstI。配对分析和扩展单倍型分析表明，多态位点之间存在随机关联(连锁平衡)。在四个不同的人群(白人、美国黑人、皮马印第安人和日本人)中测定了RFLP的变异性。BgIII RFLP在白色染色体中的频率极低。在GLUT-2基因座上观察到4个多态位点，包括EcoRI、HaeIII和2个TaqI RFLP。通过多次摄食过量的酶和…来确认每个位置更多的是家庭中的忘恩负义。EcoRI和HaeIII RFLP似乎是由于在同一位置插入和/或缺失了200个碱基的DNA。用配对分析评价各RFLP间的连锁不平衡。每对RFLP的估计单倍型频率与如果这些多态随机关联时预测的频率不同。因此，存在显著的位点间连锁不平衡现象。也有人认为，这些RFLP如果存在，可能与该基因座的突变处于连锁不平衡状态。GLUT-2基因座的RFLP频率在不同种族之间存在差异。在日本人中观察到极低的RFLP频率。这一事实要求我们在这个群体中找到一个新的有价值的RFLP。在GLUT-4基因座上观察到KpnI基因多态性。在包括日本人在内的少数受试者中，NIDDM受试者与非糖尿病受试者的等位基因频率、基因型频率和单倍型频率均无差异。对每个个体和家系中的总遗传座位(GLUT-1、-2和-4)进行扩展单倍型分析，以进一步评估这些座位对NIDDM遗传易感性的贡献。较少

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