A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus.
Hager J,
Hansen L,
Vaisse C,
Vionnet N,
Philippi A,
Poller W,
Velho G,
Carcassi C,
Contu L,
Julier C, et al.
CNRS EP 10, INSERM U358, Hôpital Saint-Louis, Paris, France.
Non-insulin-dependent diabetes mellitus (NIDDM) affects about 5% of the world population. The disease presents a polygenic mode of inheritance, but mechanisms and genes involved in late-onset NIDDM are largely unknown. We report the association of a single heterozygous Gly to Ser missense mutation in the glucagon receptor gene with late-onset NIDDM. This mutation was highly associated with NIDDM in a pooled set of French and Sardinian patients (chi 2 = 14.4, P = 0.0001) and showed some evidence for linkage to diabetes in 18 sibships from 9 French pedigrees (chi 2 = 6.63, P < 0.01). Receptor binding studies using cultured cells expressing the Gly40Ser mutation demonstrate that this mutation results in a receptor which binds glucagon with a three-fold lower affinity compared to the wild type receptor.
PMID: 7773293 [PubMed - indexed for MEDLINE]