Ghrelin Arg51Gln mutation is a risk factor for Type 2 diabetes and hypertension in a random sample of middle-aged subjects

Experimental studies have suggested that ghrelin, a novel gastrointestinal peptide hormone, could play a role in glucose homeostasis. In addition, ghrelin has been associated with beneficial haemodynamic effects in experimental settings. Since the Arg51Gln mutation changes the carboxyterminal amino acid of the mature hormone and is associated with low ghrelin concentrations, we assessed the hypothesis that Arg51Gln mutation is a risk factor for Type 2 diabetes, impaired glucose tolerance, and hypertension. Blood pressure recordings and oral glucose tolerance test were carried out in the hypertensive ( n=519) and control cohorts ( n=526) of our well-defined OPERA study. The genotypes and plasma IGF-I and IGFBP-1 concentrations of 1031 subjects were analysed. The ghrelin 51Gln allele was a risk factor for Type 2 diabetes, and the effect remained significant after adjustment for age, BMI, and study group (OR=2.53, CI: 1.11-5.75, p=0.027). In addition, the 51Gln allele was a risk factor for hypertension (OR=2.63, CI: 1.37-5.08, p=0.003). 51Gln carriers had lower concentrations of IGF-I and higher concentrations of IGFBP-1 compared to non-carriers. The ghrelin 51Gln allele could increase the risk for Type 2 diabetes and hypertension. The low IGF-I concentrations in 51Gln carriers suggest that the mechanism might be associated with low GH concentrations.