IDENTIFICATION OF 2 NOVEL AMINO-ACID POLYMORPHISMS IN BETA-CELL LIVER(GLUT2) GLUCOSE-TRANSPORTER IN JAPANESE SUBJECTS

The beta-cell/liver glucose transporter (GLUT2) gene was screened for mutations using single-strand conformation polymorphism analysis (SSCP ) in 30 Japanese subjects with non-insulin dependent diabetes mellitus (NIDDM). Analysis of all exons and adjacent intron regions identified six SSCP polymorphisms, three of which resulted in amino acid substit utions: V101I, T11OI and G519E. The V1O1I and G519E substitutions repr esent new polymorphisms in this gene. The six polymorphisms were obser ved in both NIDDM and control groups and there were no significant dif ferences in allele frequencies between groups. A portion of the insuli n receptor substrate 1 gene in 30 NIDDM subjects and in normal control subjects was also screened for mutations. Two SSCP variants that chan ge the sequence of the protein, Delta S686/687 (deletion of the codons for serine-686 and 687) and G972R, were identified in two different N IDDM subjects, both whom were also heterozygous for the V1O1I polymorp hism in GLUT2. The GLUT2 and IRS1 amino acid polymerphisms did not sho w a simple pattern of co-inheritance with NIDDM in the families of the se subjects suggesting that neither polymorphism is sufficient to caus e NIDDM but may increase diabetes-susceptibility through their interac tion with other loci and environmental factors.