Linkage study of the glucagon receptor gene with type 2 diabetes mellitus in Italians.

Abstract

Type 2 diabetes mellitus (T2DM) is a common complex trait disorder. Multiple genome scans have identified different loci in linkage with T2D, including a locus on chromosome 17q24-25. Because the glucagon receptor gene ( GCR ) resides on chromosome 17q25, it might be responsible for the linkage identified in the same region. In a combined French-Sardinian study of GCR , there is an association of Gly 40 Ser mutation with T2DM, confirmed by a UK study but not by others. Our goal was to study this selected region of chromosome 17 in a group of Italian patients with late- and early-onset T2DM by genotyping the microsatellites D17S801, D17S937, and D17S1806 and by performing nonparametric multipoint linkage analysis (Merlin 2000-2002) with allele frequencies calculated from sib-pairs data. We recruited from the center of Italy late-onset sib pairs with T2DM and families with maturity-onset diabetes of the young/early-onset T2DM (N = 503). The linkage analysis at chromosome 17q25 reported no positive lod scores in the total T2D sib pairs, in the late-onset T2D group, and in the early-onset T2D group. Although the study does not show evidence for linkage in this chromosomal region in our Italian cohort, we cannot a priori exclude the possibility of an allelic or genotypic association. Nevertheless, we may conclude that GCR does not play a major role in the pathogenesis of T2DM in Italians.

• Authors: Claudia Gragnoli, Claudio Gragnoli, Edrice Milord, Joel Francis Habener
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 54 Issue 6 Pg. 786-7 (Jun 2005) ISSN: 0026-0495 [Print] United States
• PMID: 15931615 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Glucagon

Topics

• Diabetes Mellitus, Type 2 (etiology, genetics)
• Genetic Linkage
• Humans
• Receptors, Glucagon (genetics)