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

Activins are members of the transforming growth factor-a superfamily. They have a wide range of biological effects on cell growth and differentiation. For transmembrane signaling, activins bind directly to activin receptor ty pe 2A (ACVR2A) or 2B (ACVR2B). Transgenic and knock-out mice for the ACVR2B gene display various endocrine pancreas-related abnormalities, including i slet 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 diabete s or found in affected sib pairs from families with type 2 diabetes. Mutati on screening of the coding sequence in MODY probands and in a family with s evere type 2 diabetes, including a case of pancreatic agenesis, showed sing le 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 C aucasian population.