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 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.
Nuffield Department of Surgery, Wellcome Trust Centre for Human Genetics, Headington, Oxford, UK.
S C
SC
Gough
P J
PJ
Saker
L E
LE
Pritchard
T R
TR
Merriman
M E
ME
Merriman
B R
BR
Rowe
S
S
Kumar
T
T
Aitman
A H
AH
Barnett
R C
RC
Turner
D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D016640:Diabetes, Gestational / Q000235:genetics*; D005215:Fasting; D005260:Female; D018703:Founder Effect; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics; D008297:Male; D009154:Mutation; D011247:Pregnancy; D018027:Receptors, Glucagon / Q000235:genetics*; D006113:United Kingdom
D018027:Receptors, Glucagon