Mutation of the glucagon receptor gene and diabetes mellitus in the UK: association or founder effect?

Journal article

Recent evidence suggests that a mutation of the glucagon receptor (GCG-R) gene is involved in the development of type 2 diabetes in French patients. We have examined patients from three geographically distinct regions in the UK and found the GGT40 (Gly) to AGT40 (Ser) mutation 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 controls and have therefore replicated association of the GCG-R mutation with classical type 2 diabetes (Fisher's exact test p = 0.008). An increased frequency of the mutation of the GCG-R gene was also found in probands of type 1 (insulin dependent) diabetic multiplex (affected sib pair) families, (10/404, 2.5%). However, a lack of preferential transmission from parents heterozygous for the mutation, to affected type 1 diabetic sibs may suggest population stratification. This in turn cannot be excluded as an alternative explanation for the difference in frequency of the GCG-R gene mutation between subjects with type 2 diabetes and normal controls.

Authors: Gough, S; Saker, P; Pritchard, L; Merriman, T; Merriman, M

• Journal: Human molecular genetics
• Volume: 4
• Issue: 9
• Pages: 1609-1612
• Publication date: 1995-09-01
• DOI: 10.1093/hmg/4.9.1609
• EISSN: 1460-2083
• ISSN: 0964-6906
• Language: English
• Keywords: Fasting; Diabetes Mellitus, Type 2; Male; Founder Effect; Mutation; Receptors, Glucagon; Diabetes Mellitus, Type 1; Great Britain; Female; Heterozygote; Hyperglycemia; Genetic Linkage; Pregnancy; Humans; Diabetes, Gestational