NON-LINKAGE OF THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR GENE WITH MATURITY-ONSET DIABETES OF THE YOUNG

Glucagon-like peptide-1 (GLP-1) is a hormone derived from the preprogl ucagon molecule that is secreted by intestinal L cells and stimulates insulin secretion from betacells. The GLP-1 receptor is a candidate ge ne for diabetes mellitus, as mutations may induce the impaired insulin response that is a characteristic feature of NIDDM. To study the rela tionship between the GLP-1 receptor gene and NIDDM, linkage of a micro satellite polymorphism flanking the GLP-1 receptor gene with diabetes was investigated in three Caucasian families with MODY and in the nucl ear families of 12 NIDDM probands. A cumulative LOD score - 8.50 exclu des linkage in these MODY pedigrees. A LOD score of - 1.24 in the NIDD M nuclear pedigrees makes linkage improbable. Mutations in or near the GLP-1 receptor gene are unlikely to be the major cause of the inherit ed predisposition to NIDDM in Caucasian pedigrees, but we cannot exclu de a role for this locus in a polygenic model or a major role in some pedigrees.