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 preproglucagon molecule that is secreted by intestinal L cells and stimulates insulin secretion from beta cells. The GLP-1 receptor is a candidate gene for diabetes mellitus, as mutations may induce the impaired insulin response that is a characteristic feature of NIDDM. To study the relationship between the GLP-1 receptor gene and NIDDM, linkage of a microsatellite polymorphism flanking the GLP-1 receptor gene with diabetes was investigated in three Caucasian families with MODY and in the nuclear families of 12 NIDDM probands. A cumulative LOD score -8.50 excludes linkage in these MODY pedigrees. A LOD score of -1.24 in the NIDDM nuclear pedigrees makes linkage improbable. Mutations in or near the GLP-1 receptor gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees, but we cannot exclude a role for this locus in a polygenic model or a major role in some pedigrees.
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK.
Y
Y
Zhang
J T
JT
Cook
A T
AT
Hattersley
R
R
Firth
P J
PJ
Saker
M
M
Warren-Perry
M
M
Stoffel
R C
RC
Turner
D001483:Base Sequence; D004247:DNA / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005796:Genes; D008040:Genetic Linkage; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics*; D018027:Receptors, Glucagon
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D015345:Oligonucleotide Probes; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D004247:DNA