ABSENCE OF ASSOCIATION BETWEEN THE GLY(40)-]SER MUTATION IN THE HUMANGLUCAGON RECEPTOR AND JAPANESE PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS OR IMPAIRED GLUCOSE-TOLERANCE

We investigated whether a G(123)-->A mutation causing a Gly(40)-->Ser substitution in exon 2 of the human glucagon receptor gene, which has been reported to be associated with non-insulin-dependent diabetes mel litus (NIDDM) and impaired glucose tolerance (IGT) in France and Sardi nia with a prevalences as high as 4.6% and 8.3%, respectively, is asso ciated with Japanese patients with glucose intolerance. This mutation was not found in 242 unrelated Japanese patients with NIDDM or 23 with IGT by screening by the polymerase chain reaction-restriction fragmen t length polymorphism method. We also performed single-stranded confor mational polymorphism analysis to search for new mutations in this gen e associated with glucose intolerance. We found no mutations by examin ing all the 13 exons from 30 selected patients with NIDDM who had at l east 2 diabetic first-degree relatives. These patients were also scree ned for the common polymorphism at codon 155 reported previously, but none were found to carry it. The absence of the mutation and polymorph ism, which are common in French and Sardinian NIDDM or IGT patients, i n Japanese indicates the existence of marked ethnic differences.