HEPG2 ERYTHROCYTE GLUCOSE-TRANSPORTER (GLUT1) GENE IN NIDDM - A POPULATION ASSOCIATION STUDY AND MOLECULAR SCANNING IN JAPANESE SUBJECTS/

To evaluate the role of mutations in the glucose transporter (GLUT1) g ene in Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM), we first conducted a population association study using the X baI polymorphism of the gene. A polymerase chain reaction (PCR)-based assay was developed and used for the analysis. When analysed in 91 dia betic patients and 87 non-diabetic control subjects, the distribution of the genotype frequency was significantly different between the two groups (p = 0.0025). The (-) allele was significantly associated with NIDDM (odds ratio 2.317, 95% confidence interval 1.425-3.768). To iden tify possible mutation(s) in the GLUT1 gene, which was in linkage dise quilibrium with the (-) allele, all ten exons of the gene were analyse d by PCR single-strand conformation polymorphism (SSCP) analysis in 53 diabetic patients with at least one (-) allele. Variant SSCP patterns were detected in exons 2, 4, 5, 7, 9 and 10. Sequence analysis reveal ed that all the variants represented silent mutations. One of the vari ants in exon 2, GCT (Ala(15)) --> GCC(Ala), created a HaeIII restricti on site, This polymorphism was common in Japanese subjects with hetero zygosity of 0.36 and polymorphism information content 0.29. We conclud e that the structural mutation of GLUT1 is rare and not likely to be a major genetic determinant of NIDDM in Japanese subjects. The XbaI (-) allele of the GLUT1 gene appeared to be a genetic marker of NIDDM in Japanese subjects. The possibility of the presence of mutation(s) in t he regulatory region of the gene or in another locus nearby could not be excluded.