A common variant in the Melatonin Receptor 1B gene (MTNR1B) is associated with increased risk of impaired fasting glucose (IFG) in obese youth

OBJECTIVE: To explore the role of MTNR1B rs10830963 and G6PC2 rs560887 variants in the pathogenesis of impaired fasting glucose (IFG) in obese adolescents. DESIGN AND METHODS: 346 Caucasians, 218 African Americans and 217 Hispanics obese children and adolescents underwent an oral glucose tolerance test (OGTT) and 518 underwent the evaluation of insulin secretion by the oral minimal model (OMM). Also, 274 subjects underwent a second OGTT after 3.0±2.1 years. RESULTS: The MTNR1B rs10830963 variant was associated with higher fasting glucose levels and lower dynamic beta cell response in Caucasians and Hispanics (p<0.05) and conferred an increased risk of showing IFG to Caucasians (p=0.05), African Americans (p=0.0066) and Hispanics (p=0.024). Despite the association between the G6PC2 rs560887 and higher fasting glucose levels (p<0.05), there was no association between this variant and IFG at baseline or at follow-up (all p>0.10). CONCLUSIONS: We show for the first time in obese youth that the MTNR1B variant is associated with an increased risk of IFG.