MUTATION OF THE GLUCAGON RECEPTOR GENE AND DIABETES-MELLITUS IN THE UK - ASSOCIATION OR FOUNDER EFFECT

Recent evidence suggests that a mutation of the glucagon receptor (GCG -R) gene is involved in the development of type 2 diabetes in French p atients, We have examined patients from three geographically distinct regions in the UK and found the GGT(40) (Gly) to AGT(40) (Ser) mutatio n to be present in 15/691 (2.2%) of patients with type 2 (non-insulin dependent) diabetes and 1/425 (0.2%) of geographically matched control s and have therefore replicated association of the GCG-R mutation with classical type 2 diabetes (Fisher's exact test p = 0.008). An increas ed frequency of the mutation of the GCG-R gene was also found in proba nds of type 1 (insulin dependent) diabetic multiplex (affected sib pai r) families, (10/404, 2.5%), However, a lack of preferential transmiss ion from parents heterozygous for the mutation, to affected type 1 dia betic sibs may suggest population stratification. This in turn cannot be excluded as an alternative explanation for the difference in freque ncy of the GCG-R gene mutation between subjects with type 2 diabetes a nd normal controls.