title: No evidence for linkage or for diabetes-associated mutations in the activin type 2B receptor gene (ACVR2B) in French patients with mature-onset diabetes of the young or type 2 diabetes.
abstract: Activins are members of the transforming growth factor-beta superfamily. They have a wide range of biological effects on cell growth and differentiation. For transmembrane signaling, activins bind directly to activin receptor type 2A (ACVR2A) or 2B (ACVR2B). Transgenic and knock-out mice for the ACVR2B gene display various endocrine pancreas-related abnormalities, including islet hypoplasia and glucose intolerance, demonstrating the crucial role of ACVR2B in the regulation of pancreas development. We have thus examined the contribution of this factor to the development of mature-onset diabetes of the young (MODY) and type 2 diabetes. No evidence of linkage at the ACVR2B locus has been detected in MODY families with unknown etiology for diabetes or found in affected sib pairs from families with type 2 diabetes. Mutation screening of the coding sequence in MODY probands and in a family with severe type 2 diabetes, including a case of pancreatic agenesis, showed single nucleotide polymorphisms that did not cosegregate with MODY and were not associated with type 2 diabetes. Our results indicate that ACVR2B does not represent a common cause of either MODY or type 2 diabetes in the French Caucasian population.
authors.affiliation: Institute of Biology-Centre National de la Recherche Scientifique CNRS 8090, Institut Pasteur, Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Dupont
authors.forename: E H
authors.initials: EH
authors.lastname: Hani
authors.forename: C
authors.initials: C
authors.lastname: Cras-Méneur
authors.forename: F
authors.initials: F
authors.lastname: De Matos
authors.forename: S
authors.initials: S
authors.lastname: Lobbens
authors.forename: C
authors.initials: C
authors.lastname: Lecoeur
authors.forename: M
authors.initials: M
authors.lastname: Vaxillaire
authors.forename: R
authors.initials: R
authors.lastname: Scharfmann
authors.forename: P
authors.initials: P
authors.lastname: Froguel
mesh_terms: D030301:Activin Receptors, Type II; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons; D005602:France; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008126:Lod Score; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017978:Receptors, Growth Factor / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D017978:Receptors, Growth Factor; D030301:Activin Receptors, Type II