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

Claudio Gragnoli, Edrice Milord, Joel Francis Habener

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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 40Ser 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.

Original languageEnglish (US)
Pages (from-to)786-787
Number of pages2
JournalMetabolism: Clinical and Experimental
Issue number6
StatePublished - Jun 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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