|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1990 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1989 : ¥1,500,000 (Direct Cost : ¥1,500,000)
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
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