A MUTATION IN THE GLUCAGON RECEPTOR GENE (GLY40SER) - HETEROGENEITY IN THE ASSOCIATION WITH DIABETES-MELLITUS

A possible pathogenic mutation in the glucagon receptor gene causing a Gly to Ser change at codon 40 (Gly40Ser) was reported to be associate d and linked with non-insulin-dependent diabetes mellitus (NIDDM), in France and Sardinia. Since the frequency of the mutation (Gly40Ser), a bout 5% in the French population of familial NIDDM and 8% in randomly chosen diabetic patients in Sardinia, was much higher than that of any of the previously reported mutations in candidate genes, it is import ant to clarify whether the contribution of this mutation to NIDDM is u niversal. In this study, we investigated the association of this mutat ion with diabetes mellitus in a large number of Japanese diabetic pati ents (383 NIDDM and 53 insulin-dependent diabetic patients) by polymer ase chain reaction-restriction fragment length polymorphism analysis. None of the Japanese diabetic patients showed Gly40Ser mutation and th e association of this mutation with NIDDM was significantly different (p < 4 . 10(-5) vs French, p < 3 . 10(-6) vs Sardinian by Fisher's exa ct test). The results not only indicate that the mutation plays little , if any, role in susceptibility to diabetes in Japan, but also indica te the genetic heterogeneity in NIDDM and further emphasize the import ance of studies on genetic susceptibility to NIDDM and other complex t raits in different ethnic groups.