HIGH-FREQUENCY OF POLYMORPHISM BUT NO MUTATIONS FOUND IN THE GLUT1 GLUCOSE-TRANSPORTER GENE IN NIDDM AND FAMILIAL OBESITY BY SSCP ANALYSIS

To evaluate whether a structural defect in the human glucose transport er gene GLUT1 could be involved in the aetiology of insulin resistance , a key factor of noninsulin-dependent diabetes mellitus (NIDDM) and o besity, we performed single-strand conformation polymorphism (SSCP) an alysis in 40 subjects (20 NIDDM patients and 20 subjects with familial obesity). The GLUT1 gene, which is involved in basal glucose transpor t in most tissues, consists of ten exons and encodes a 492 amino acid protein. Population studies have shown a strong association between th e X1 allele of an XbaI restriction fragment length polymorphism of the GLUT1 gene and NIDDM. We therefore performed SSCP analysis in NIDDM s ubjects known to carry at least one X1 allele. Variant SSCP patterns w ere detected in exons 2, 4, 5 and 9. Sequence analysis of the SSCP var iants revealed the presence, in all exons examined, of silent mutation s consisting of single-nucleotide substitutions with no amino acid cha nges. Both NIDDM and obese patients showed a high frequency of polymor phism in the sequence (50% and 35%, respectively). We conclude that th e GLUT1 gene is unlikely to play a role in the aetiology of NIDDM and obesity. However, the strong association between the GLUT1 gene and NI DDM, together with the recent family studies showing linkage between c hromosome Ip and NIDDM warrant further studies on this chromosomal reg ion.