Endocrine Abstracts

Ghrelin is an orexigenic hormone, the endogenous ligand of the previously orphan growth-hormone-secretagogue receptor (GHS-R). Recently, it has been reported that pancreatic beta-cells are replaced by ghrelin-producing cells in a diabetic mice model implicating these genes as attractive candidates in the aetiology of type 2 diabetes (T2D) (PNAS;101:2924). The ghrelin gene is located at 3p25-26 and its cognate receptor at 3q26. We aimed to test for an association of these two genes with T2D in a case-control study in a French population. This study consisted of 740 subjects with T2D and 932 non-diabetic controls. Five tagged single nucleotide polymorphisms (SNPs) were selected and genotyped in the ghrelin gene by mass spectrometry SEQUENOMTM, two in the promoter and three in the coding region which do not modify the mature ghrelin amino-acid sequence. Our results do not suggest association of these SNPs with T2D (SNP and haplotype p>0.05). However, we recently reported the C247A SNP to be associated with higher body mass index (BMI) in obese children (JCEM;87:4005), suggesting a role for ghrelin in this intermediate phenotype of type 2 diabetes. Using haplotype trend regression analysis, the ghrelin haplotypes were found to be associated with the observed BMI distribution in the diabetics (n=614, overall p=0.0084) but not in the control group (n=268, p=0.2). Further work is currently in progress to complete this study for the GHS-R gene to define the role of ghrelin and its receptor in T2D. In summary, we have not found an association of the genetic variation in the ghrelin gene and T2D; however, our results support the speculation that weight regulation may be affected by the genetic variation observed in the ghrelin gene in patients with diabetes.

This study is supported by Diabetes UK.