title: A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus.
abstract: 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.
authors.affiliation: CNRS EP 10, INSERM U358, Hôpital Saint-Louis, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Hager
authors.forename: L
authors.initials: L
authors.lastname: Hansen
authors.forename: C
authors.initials: C
authors.lastname: Vaisse
authors.forename: N
authors.initials: N
authors.lastname: Vionnet
authors.forename: A
authors.initials: A
authors.lastname: Philippi
authors.forename: W
authors.initials: W
authors.lastname: Poller
authors.forename: G
authors.initials: G
authors.lastname: Velho
authors.forename: C
authors.initials: C
authors.lastname: Carcassi
authors.forename: L
authors.initials: L
authors.lastname: Contu
authors.forename: C
authors.initials: C
authors.lastname: Julier
mesh_terms: D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D005934:Glucagon / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018027:Receptors, Glucagon / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D018027:Receptors, Glucagon; D005934:Glucagon