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  • Title: Association of a MTNR1B gene variant with fasting glucose and HOMA-B in children and adolescents with high BMI-SDS.
    Author: Holzapfel C, Siegrist M, Rank M, Langhof H, Grallert H, Baumert J, Irimie C, Klopp N, Wolfarth B, Illig T, Hauner H, Halle M.
    Journal: Eur J Endocrinol; 2011 Feb; 164(2):205-12. PubMed ID: 21059861.
    Abstract:
    CONTEXT: Genome-wide association studies have shown that the melatonin receptor 1B (MTNR1B) gene locus is strongly associated with fasting glucose and β-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 β-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 β-estimates. The P value for the genotype × 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.
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