Association of a MTNR1B gene variant with fasting glucose and HOMA-B in children and adolescents with high BMI-SDS

Context: Genome-wide association studies have shown that the melatonin receptor 1B (MTNR1B) gene locus is strongly associated with fasting glucose and beta-cell function. However, data are rather limited to the adult population and normal-weight children. So far, little is known whether similar associations are present in overweight and obese children and adolescents. Objective: The aim is to investigate an MTNR1B polymorphism in a sample of 310 overweight and obese children and adolescents (mean body mass index standard deviation score (BMI-SDS)): 2.74 (+/- 0.55), mean age: 14 (+/- 2) years), who participated in a short-term weight-loss program based on energy reduction, physical activity, and behavior therapy. Methods: We investigated an association between genotype and fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and of beta-cell function (HOMA-B), and anthropometric parameters and their change during intervention. Results: The minor G allele of polymorphism rs10830963 was significantly associated with increased fasting glucose (0.205 mmol/l, P<0.0001) and decreased HOMA-B (-0.353, P<0.0001). Categorizing the sample into BMI-SDS groups, these significant associations were abolished in children with BMI-SDS below 2.5 but remained in those with higher BMI-SDS values with stronger beta-estimates. The P value for the genotype x BMI-SDS category interaction was 0.012 for fasting glucose and 0.083 for HOMA-B. There was no significant association between genotype and anthropometric parameters and their change during intervention. Conclusions: This is the first single study, replicating the association between the MTNR1B locus and diabetes-related traits in overweight and obese children and adolescents. The effect sizes in children and adolescents seem to be stronger than in adults and differed among BMI-SDS categories. European Journal of Endocrinology 164 205-212